The management of KTR can be divided into two phases:
An early post-operative phase when prevention of acute rejection, optimization of graft function and prevention of opportunistic infection are paramount
b. a later phase when the aims are to preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression – malignancy, infection and premature cardiovascular disease.
Transplantation place, staff should be available, frequency set as standard protocol, most
Frequent in the first month ,reduced gradually to 1-2 times in next month then weekly in coming third month ,then monthly up to one year , then every 3months or more depend on patient condition.
Patient access:
Should have an open access to transplant team, on line access and patient information written and instruction given Cleary?
Patient should have an integrated annual examination with multi-disciplinary team Immunosuppression regimen: Induction therapy:
With biological agents should be administered to all KTRs.
In an interleukin-2 receptor antagonist in low immunological risk.
T-cell (lymphocyte) depleting antibodies in higher immunological risk. TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor avoidance.
CNI should be started at the time of transplantation and not delayed until the graft is functioning. Maintenance immunosuppression:
Calcineurin inhibitor (and an anti-proliferative agent (MMF), with or without corticosteroids in low and medium immunological risk KTRs.
Minimum target levels for CNIs in uncomplicated renal transplantation after 3 months
Not tolerant KTR to tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second line agents such as cyclosporine, sirolimus, everolimus, or belatacep.
Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients. If not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less). Monitoring of immunosuppression:
Should be done initially 3 times per week, using trough (TAC and Sirolimus) OR Co or C2 for CSA. Acute rejection:
Biopsy should be done, protocol biopsy in case of persistent DGF.
C4d and SV40 staining should be performed.
HLA specific antibodies. Treatment of acute rejection:
Borderline acute cellular rejection should be treated in the context of acute graft dysfunction.
High dose intravenous corticosteroids should be the first line treatment for acute cellular rejection.
Maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type.
Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III).
AMR: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib.
After AR – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximized. Chronic Allograft Injury:
By biopsy, C4d and SV 40 should be done.
HLA antibodies. Treatment of chronic allograft injury
Treat any underlying cause (ABR or CMR, CNI toxicity), Preventive measures for CKD. Renal biopsy in chronic allograft injury:
We suggest that a renal transplant biopsy is indicated:
· If there is a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection (BPAR) (1C)
· Every 7-10 days during delayed graft function (DGF) (2C)
· If expected renal function is not achieved within 4-8 weeks (2D)
· If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol) (2C) Hypertension:
Regular check, keep below 140/90, no specific antihypertension, caution with ACI in first 3months. Dyslipidemia:
As in general population should be controlled, avoid high dose simvastatin with CNI and CCB. Diabetes mellitus:
Screen regularly, use WHO criteria to diagnose it, follow for complication. Ischemic heart disease:
KTRs receive standard treatment for IHD, including thrombolysis, revascularization, and secondary prevention. Lifestyle measures
We suggest that advice on healthy lifestyle, DIET, WEIGHT, BMI less 25 kg/m2, exercise .avoid smoking and non-prescribed medication. Screening for cancer:
· Screening should be similar to the general population for cervical, breast, colon and prostate cancer
· Screening is not recommended for renal cell carcinoma.
Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant.
To cover their skin in direct sunlight and to use total sunblock, (Sun Protection Factor ≥50). Vaccination:
We recommend that KTRs:
· Should be vaccinated with inactivated viruses as per the normal population (1D)
· Should receive annual influenza vaccination unless contraindicated.
Should have hepatitis B surface antibody (HBsAb) levels rechecked annually and be revaccinated if antibody titres fall below 10 mIU/mL (2D)
· Should not receive live attenuated vaccines (2C)
· Should receive pneumococcal vaccine and a booster every five years. Cytomegalovirus (CMV) disease Guideline:
· Prophylaxis should be continued for 3-6 months, until immunosuppression has been reduced to long-term maintenance level (1B)
· Treatment should be administered for 6 weeks after treatment with a TDA. EBV infection:
Recommend that immunosuppression should be reduced or stopped following the development of post-transplant lymphoproliferative disease.
All high risk (D+ /R- ) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year (2C)
· EBV viral load should be monitored after the treatment of rejection (2C)
· Total immunosuppression should be reduced when EBV tires rise significant.
Varicella-susceptible KTRs (i.e. VZV IgG negative) with primary exposure to VZV should receive intravenous immunoglobulin, ideally within 96 hours, but up to a maximum of 10 days following exposure. If unavailable or after 10 days, oral acyclovir should be prescribed for seven days.
VZV infection:
· Primary infection (chickenpox) should be treated with intravenous acyclovir or oral valaciclovir until the lesions scab over (1C)
· Uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over (1D)
· Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with intravenous acyclovir until the lesions scab over, together with a reduction in immunosuppression. BK nephropathy:
We recommend that confirmed BK nephropathy should be treated by reduction in immunosuppression.
Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml.
Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40. Pneumocystis jirovecii infection:
-All patients with confirmation (microscopy or PCR) of Pneumocystis jirovecii in respiratory secretions should be treated for 14 to 21 days with co-trimoxazole orally or intravenously (15-20mg/kg in three or four divided.
Contraindications to treatment with co-trimoxazole should receive pentamidine (4mg/kg/day intravenously) (2B)
· Adjunctive glucocorticoid in severe disease (2D)
· All patients should receive 3-6 months of treatment with co-trimoxazole 480mg daily for prophylaxis following renal transplantation. Osteoporosis:
DEXA scanning if eGFR >30.
Tertiary hyperparathyroidism:
· Severe hyperparathyroidism should be treated prior to transplantation.
Cinacalcet can be used. Treatment of gout:
If stone, gout and tophi,
Neither allopurinol nor febuxostat should be administered with azathioprine.
Acute gout may be treated with brief a course of oral prednisolone. (2D)
· Colchicine is an effective treatment for gout in KTR. Anemia:
We suggest that chronic anemia should be managed in the same way as other patients with CKD. Polycythemia: initial treatment should be with ACEIs or ARBs.
Venesection may be used in refractory cases. Conception and contraception (female):
Stop MMF and mTor prior to pregnancy, delay pregnancy for one year.
KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth of the baby unless there are contraindications.
All immunosuppressive drugs other than m-TORi can be used in male KTRs. Sexual dysfunction
Close liaison with local andrology service is recommended.
· Sildenafil is safe and effective in male KTR not taking nitrates.
Level of evidence V.
Rehab Fahmy
2 years ago
BTS guidelines:
For management of patients post kidney transplant from all sides:
1-infrastructure of hospital and clinic
2-Counselling of patients
3-induction and maintenance immunosuppression
4-infections
rejection treatment
contraception
level 5 evidence
Nasrin Esfandiar
2 years ago
This is a guideline for post-up care in patient with kidney
transplantation.
Results of laboratory test should be available and then reviewed
within 24 hours.
Frequency of clinical visit:
2-3 /week first months 1-2 /week for 2-3 month 2-4 weeks for 4-
6 months,4-6 week weeks for 6-12 months and then 3-6
monthly.
A detailed review is needed annually.
Diagnosis of non-adherence is important and needs to prevent.
Induction immunosuppression in low risk patients includes IL2-RA and for high risk recipients includes lymphocyte depleting antibodies.
Maintenance immunosuppression includes CNI (tacrolimus is
close) and anti-proliferative agent (usually MMF unless
contraindicated) ± steroids.
-CNI levels should be checked regularly.
-Generic drugs should not be used unless being proven
bioequivalent.
Acute rejection should be diagnosed by renal biopsy.
Recipients with DGF should have protocol biopsy and SV40 and C4d staining is necessary.
In addition, anti HLA-Abs are needed to be evaluated.
The first line treatment for acute rejection consists high- dose
corticosteroids.
Refractory TCMR needs treatment by lymphocyte depleting agents (TDAs).
-ABMR treatment modalities are plasmapheresis IVIG
rituximab, TDAs or bortezomib.
Renal biopsy in needed with chronically deteriorating TX with
C4d and SV40 staining to diagnosis chronic allograft injury(CAN).
Treatment of CAN:
1- In case of evidence for CNI toxicity reduction or withdrawal of it suggested.
2- In case of evidence of immune injury immunosuppression
should be intensified.
Control of BP is suggested at each visit.
BP should be less than140/90 and in case of albuminuria or
proteinuria should be less than 130/80 mmHg.
RAAS inhibitors should be used with caution during the first
3 months.
Hyperlipidemia is suggested to be evaluated and control to
reduce CVD risk.
PTDM should be diagnosed and treated appropriately.
Appropriate treatment for IHD in suggested. Smoking should be stopped after the transplantation. All recipients should follow a healthy lifestyle including a healthy diet, ideal body weight, appropriate physical activity, avoidance of alcohol over the counter or herbal medicine consumption. Cancer screening is suggested for all recipients. Annual influenza vaccine is recommended. CMV prophylaxis is recommended for the first 3-6 month and 6 weeks after TDA usage. Appropriate diagnosis and treatment for CMV is suggested. Screening for EBV is suggested for high risk (D+/R-) recipients. Screening for BK virus nephropathy and treatment by immunosuppression is recommended.
Oral prophylaxis for pneumocystis jirovecii and proper treatment with cotrimoxazole is suggested. Osteoporotic recipients are considered for steroid-avoidance immunosuppression. Appropriate treatment for hyperthyroid is suggested. ACEIs or ARBs are Recommended for post TX polycythemia. One-year wait is suggested before conception in TX recipients. MMF and m-TORi should be stopped before conception. Sexual dysfunction should be evaluated and treated. · The level of evidence is 5 for guidelines.
Ghalia sawaf
2 years ago
Summary of Clinical Practice Guidelines for the Post-Operative Care of the Kidney Transplant Recipient
Organisation of Outpatient Follow-up Clinic infrastructure
We suggest that the following infrastructure should be in place for KTR follow up (2D):
A consultant-level health care professional should be available for every transplant clinic
KTRs should be reviewed in a dedicated outpatient area
1. The results of blood tests (including drug levels if possible) should be available within 24 hours
2. A formal mechanism should exist for results review by health care professionals within 24 hours of a clinic appointment
3. There should be access to a multidisciplinary renal team including pharmacist, dietician, social worker and psychologist
4. Patient care should be planned along principles set out in the National Service Framework and “Kidney Health Delivering Excellence”
KTR: Clinic frequency
We suggest that uncomplicated patients may be reviewed progressively less frequently (2C)
• 2-3 times weekly for the first month after transplantation
• 1-2 times weekly for months 2-3
• Every 2-4 weeks for months 4-6
• Every 4-6 weeks for months 6-12
• 3-6 monthly thereafter
KTR: Patient access
We suggest that all patients should have access to support services and results. (2C)
1. All patients should have the option of on-line access to their results via the “Patient View” service
2. All patients should have open access to the renal transplant outpatient service and have an established point of contact for enquiries
3. Patient information should be available in both written and electronic formats
KTR: Chronic transplant care review
We suggest that a detailed review should be performed annually post-operatively (2C)
• A process should exist for patient review on an annual basis in a different format of clinic according to the “Care plan model”
• This should be a patient-centred clinic, facilitated by a health care professional
• It should address concerns in medical, social, psychological and sexual domains
• Access to a renal dietician, social worker, specialist renal pharmacist and/or psychologist should be readily available from this clinic
• This process should proceed in parallel with formal medical review
Kidney Transplant Recipient: Non-adherence
We suggest that it is important to prevent and detect non-adherence in kidney transplant recipients. (2C)
• Factors associated with non-adherence should be identified
• An established interventional pathway should be in place for those at high risk of or with proven nonadherence
• Pathways should be in place for paediatric KTRs in transition and for adolescent KTRs
Kidney Transplant Recipient: Immunosuppressive treatment –
We recommend that the patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression (1D)
Induction immunosuppression
We recommend induction therapy should take into account the following:
Immunosuppressive drugs should be started before or at the time of renal transplantation (1B)
• Induction therapy with biological agents should be administered to all KTRs. In patients at low immunological risk this will generally involve an interleukin-2 receptor antagonist (IL2-RA).
• Recipients at higher immunological risk may be considered for T-cell (lymphocyte) depleting antibodies (TDAs)(1B)
• Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance (1C)
• We suggest that a CNI should be started at the time of transplantation and not delayed until the graft is functioning (2C)
Maintenance immunosuppression
• We recommend that maintenance immunosuppression should normally consist of a calcineurin inhibitor (CNI) and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs (1B)
• We suggest that low-medium dose tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice in patients also taking steroids who are low and medium immunological risk and are not at high risk of developing post transplant diabetes mellitus (PTDM) (2C)
• We suggest that mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B)
• We suggest that slow release tacrolimus may be used as an option as second line agents for patients who suffer intolerable side effects related to peak dose toxicity (2C)
• We suggest that KTRs who are unable to tolerate tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second line agents such as ciclosporin, sirolimus, everolimus, or belatacept (1B)
• We suggest that MPA-based drugs should be the first-line antiproliferative agent, in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B)
• We suggest that mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (Myfortic®) provide equivalent maintenance immunosuppression (2B)
• We suggest that steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients (2B)
• We suggest aiming for minimum target levels for CNIs in uncomplicated renal transplantation after 3 months (2C)
• We suggest that CNIs should not be withdrawn (2B)
• We suggest that if steroids are not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less) (2C)
Monitoring of immunosuppression
We suggest that long-term monitoring of immunosuppression levels is required as follows:
• Tacrolimus and ciclosporin levels should be monitored.
• The initial frequency should be three times a week.
• Levels should also be checked when any medication with possible interactions is prescribed, the dosage is changed, the formulation is changed, or when there is unexplained graft dysfunction (2C)
• Tacrolimus should be monitored by the trough (C0) level, while ciclosporin can be monitored by either C0 or 2hour post dose (C2) level (2C)
• Tacrolimus and ciclosporin levels should be available within 24 hours of taking blood samples in the first three months after transplantation (2D)
• The utility of monitoring mycophenolic acid (MPA) C0 levels is uncertain (2D)
• Sirolimus should be monitored by the C0 trough level (2C)
Prescribing and the use of generic agents ;
• they should not be used unless they have been shown to be bioequivalent and approved by the European Agency for the Evaluation of Medicinal Products (2D)
• We suggest that KTRs should be made aware of the existence of generics and the importance of not switching between preparations without appropriate supervision (2D)
• We suggest that drugs should be prescribed by brand name (whether branded or generic drugs are prescribed) (2D)
• We suggest that KTRs should be closely monitored after switching between generic preparations until a new steady state is established (2D)
Diagnosis of acute rejection
• We recommend that a transplant renal biopsy should be carried out before treating an acute rejection episode unless this will substantially delay treatment or pose a significant risk to the patient (1C)
• We suggest that two cores of renal tissue should be obtained at transplant biopsy since this will increase the sensitivity of the investigation (2C)
• We suggest that a 16 gauge automated core biopsy needle is used where possible to provide the best compromise between diagnostic usefulness and patient tolerance of the procedure (1C)
• We recommend that a protocol transplant renal biopsy, defined as a biopsy performed in a stable graft without clinical evidence of acute rejection, be considered in the setting of persisting delayed graft function (1C)
• We recommend that routine C4d and SV40 staining should be performed upon transplant biopsies to address other causes of graft dysfunction (2C)
• We suggest that a serum sample be sent at the time of renal biopsy (for graft dysfunction) to look for human leucocyte antigen (HLA)-specific antibodies (2C)
Treatment of acute rejection
• We suggest that borderline acute cellular rejection should be treated in the context of acute graft dysfunction (2D)
• We recommend that high dose intravenous corticosteroids should be the first line treatment for acute cellular rejection (1D)
• We suggest that maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type (2D)
• We suggest that lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III) (2C)
• We suggest that antibody mediated rejection (AMR) should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib (2C)
• We recommend that the British Transplant Society (BTS) guidelines on antibody incompatible transplantation for management of rejection in the context of antibody incompatible transplantation (1A-D)
• We suggest that – after an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximised
Diagnosis of Chronic Allograft Injury
• We recommend that early identification of graft injury is desirable to maximise the potential for intervention. A proactive and systematic approach should employed to manage graft dysfunction (1C)
• We suggest that renal function should be monitored at each clinic visit by assessment of serum creatinine and qualitative evaluation of urine protein excretion by dipstick, supplemented by spot protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR) if positive (2C)
• We suggest that renal biopsy is the optimal investigation for parenchymal causes of graft dysfunction where the cause is uncertain (2C)
• We suggest that renal biopsies in patients with chronically deteriorating function should be stained for C4d and SV40 (2C) We suggest that a serum sample should be sent at the time of renal biopsy (for graft dysfunction) to look for HLAspecific antibodies (2C)
Treatment of chronic allograft injury
We suggest that chronic allograft injury should be treated By withdrawal of calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy (2C)
• By intensification of immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection) (2C)
• In a similar fashion to other patients with chronic kidney disease (CKD), following similar preventative strategies and with timely referral to low clearance services (2D
Renal biopsy in chronic allograft injury
We suggest that a renal transplant biopsy is indicated:
• If there is a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection (BPAR) (1C)
• Every 7-10 days during delayed graft function (DGF) (2C)
• If expected renal function is not achieved within 4-8 weeks (2D)
• If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol) (2C)
Kidney Transplant Recipient: Cardiovascular Disease and Lifestyle Hypertension
• We suggest that the management of hypertension take into account that: • Blood pressure should be recorded at each clinic visit (1C)
• Clinic blood pressure should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
• Home blood pressure recordings and 24-hour ambulatory recordings may be helpful in some instances but lower BP targets should then be set (home and or ambulatory daytime measures <135/80mmHg) (2D)
• There is no evidence that any antihypertensive agent is better than any other and effort should be focused on achieving absolute blood pressure control rather than the use of individual agents (2D)
• Inhibitors of the renin-angiotensin system may be more effective in the minimisation of proteinuria but should be used with caution in the first 3 months post-transplant.(2C)
• Resistant hypertension may be due to transplant renal artery stenosis and should be investigated according to local practice (2D)
Dyslipidaemia
We suggest that the management of dyslipidaemia take into account that: • Fasting lipid levels should be measured on an annual basis in renal transplant recipients (2C)
Treatment targets should be the same as in the general population (2C)
KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease (2C)
The choice and dose of statin should take into account concurrent immunosuppression.
High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/calcium channel antagonists (2D)
Diabetes mellitus
• We suggest that the detection and treatment of diabetes should consider:
• Screening for the development of post-transplant diabetes mellitus (PTDM) by dipstick urinalysis and measurement of blood sugar level at each clinic visit (2C)
• Post-transplant immunosuppression should take into account risk factors for the development of diabetes (2C)
• The diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing (1C)
• A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression (2D)
• Post-transplant diabetes should be managed in collaboration with specialists in diabetic medicine (2D)
• All units should have a protocol for the management of post-transplant diabetes (2C)
• KTR with diabetes (either prior to transplantation or PTDM) should undergo screening for diabetic complications (retinal screening, foot care, neuropathy) in line with guidelines for non KTR patients with diabetes (2D)
Ischaemic heart disease
We suggest that KTRs receive standard treatment for ischaemic heart disease, including thrombolysis, revascularisation, and secondary prevention (2C)
Smoking cessation
We recommend that smoking should be strongly discouraged in transplant recipients (see guideline 6.4) (1A)
: Lifestyle measures
• We suggest that advice on healthy lifestyle forms a routine part of post-transplant care: • Maintenance of a healthy diet should be encouraged (2C)
• An ideal weight should be targeted (body mass index (BMI) ≤25 kg/m2) (2C)
• Weight management services should be available (2C)
• We suggest that KTRs participate in physical activity at a level similar to that recommended to age and comorbidity matched counterparts from the general population (2D)
• Alcohol consumption should be within national guidelines (2D)
• Recreational drug use should be avoided (2D)
• The use of over-the-counter medications (without discussion with clinical staff) and non-proprietary medications (e.g. herbal medicines) should be discouraged (2D)
Cytomegalovirus (CMV) disease Guideline Prophylaxis and treatment of CMV disease
We recommend:
• Prophylaxis should be continued for 3-6 months, until immunosuppression has been reduced to long-term maintenance level (1B)
• Treatment should be administered for 6 weeks after treatment with a TDA (1C)
• We suggest: All transplant units should be able to measure CMV serological status and quantify viral load (2D)
• Donor and recipient CMV status should be recorded at the time of transplantation (2D)
• Each unit should have a written protocolised CMV strategy based on prophylaxis or pre-emptive therapy (2D)
• For the treatment of mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are of equivalent efficacy (2C)
• The first line treatment of life-threatening CMV disease is intravenous ganciclovir (2D)
• Treatment duration should be determined by monitoring viral load (2C)
Epstein Barr Virus (EBV) infection
We recommend that immunosuppression should be reduced or stopped following the development of post transplant lymphoproliferative disease (PTLD) (1C)
We suggest: Both donor and recipient should have their EBV serology recorded at the time of transplantation (2D)
All high risk (D+/R-) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year (2C)
EBV viral load should be monitored after the treatment of rejection (2C)
Total immunosuppression should be reduced when EBV titres rise significantly (2C)
Varicella Zoster Virus (VZV) infection :
We recommend: Primary infection (chickenpox) should be treated with intravenous aciclovir or oral valaciclovir until the lesions scab over (1C)
Uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over (1D)
Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with intravenous a Varicella-susceptible KTRs (i.e. VZV IgG negative) with primary exposure to VZV should receive intravenous immunoglobulin, ideally within 96 hours, but up to a maximum of 10 days following exposure. If unavailable or after 10 days, oral aciclovir should be prescribed for seven days (1D)
We suggest Patients on the waiting list who are VZV IgG negative should be vaccinated prior to transplantation (2D)
Immunosuppression should be reduced during primary infection (2D)
Herpes Simplex Virus (HSV) infection
We recommend:
Superficial HSV infection should be treated with appropriate oral agents until the lesions have resolved (1D)
Systemic HSV infections should be treated with intravenous aciclovir and a reduction in immunosuppression until a response occurs and oral medication should be continued for at least 14 days (1C)
We suggest that KTRs suffering frequent recurrent HSV infection should consider oral prophylaxis
: BK virus (BKV) nephropathy
We recommend that confirmed BK nephropathy should be treated by reduction in immunosuppression (1D)
We suggest: Screening should also be carried out when renal function deteriorates in an unexplained fashion (2D)
KTRs should be screened for BKV viral load or by performing urine microscopy for decoy cells or by polymerase chain reaction (PCR) on urine or serum (2C)
Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40. Two cores containing medullary tissue should ideally be examined (2D)
Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml (2C)
There is no established specific treatment for BK nephropathy (2D)
Re-transplantation can safely be considered in patients who have BK nephropathy diagnosed in an earlier graft (2C)
Haematological Complications Anaemia
We suggest that chronic anaemia should be managed in the same way as other patients with CKD (2D)
Level v
Last edited 2 years ago by Ghalia sawaf
Wael Jebur
2 years ago
The BTS guideline detailed all aspects of acute and chronic management of kidney transplant recipient. By elaborating on assessment of adherence , induction and maintenance therapy, highlighting on high and low risk profile patients. Vaccinations and treatment of acute and chronic rejections and elucidating the updated management of other medical conditions complicating kidney transplantation such as infection, hypertension and diabetes mellitus.
Immunosuppression for kidney transplanted patients: Induction:
Biologic agents are recommended for induction therapy before or the time of transplantation.
For high immunologic risk patients ,T- lymphocyte depleting antibodies is recommended.
For low immunologic risk patients, IL-2 receptor antagonist is indicated.
T-lymphocyte depleting antibodies may be considered in calcineurin inhibitors CNi or steroid withdrawal or avoidance protocols. Maintenance protocol:
has to contain CNi and anti-proliferative agent in addition to corticosteroid which might be avoided or withdrawn after first week post transplantation in low and moderate risk patients.Its not recommended to withdraw steroid if it continued to be in use after the first month. However , its recommended to consider steroid inclusive protocol in high immunologic risk patients.
Its recommended to introduce Tacrolimus as the CNi of first choice with trough blood level of 4-8 ng/ml. An alternative to Tacrolimus in case of complicating side effects is Cyclosporin .Lowest trough level is recommended after 3 months post operatively.
Mycophenolic acid is Drug of choice as anti-proliferative , superior to Azathioprin, unless patient is not willing to consider anti-conception measures and increasingly prone to have pregnancy, then Azathioprime is indicated .there is no difference between Mycophenolate Sodium and Mycophenolate Mofetil regarding clinical profile. The Guideline addressed thoroughly the follow up and frequency of checking for trough level and renal function as per the time duration and necessity. Rejection :
Was discussed elaborately regarding risk factors, diagnosis and treatment. furthermore, different types of acute rejections, TCMR and ABMR diagnostic criteria was showcased. Moreover, histologic criteria and importance of C4d was demostrated.
Treatment for TCMR including first line of methylprednisolon and second line ATG was discussed in details.
For ABMR with its complicated presentation and diagnostic criteria , the guideline detailed the management points with Plasmapharesis , Retuximab, IVIg, Bortezomibe and Eculizumab. Chronic Rejection:
was reviewed in depth , demonstrating the best tool to diagnose and manage thoroughly.
Hussein Bagha baghahussein@yahoo.com
2 years ago
The summary of clinical practice guidelines for the post-operative care of the kidney transplant recipient
Kidney transplant recipient (KTR): Organization of outpatient follow-up KTR: Clinic infrastructure
The transplant clinic should follow the following requirements:
A consultant-level health care professional
A dedicated outpatient area
A quick turn over of blood test results, that should be reviewed by health care professionals within 24 hours
A multidisciplinary renal team – pharmacist, dietician, social worker, psychologist
KRA: Clinic frequency
Patients need to be followed up as follows:
2-3 times weekly – for the first month after transplantation
1-2 times weekly – for the 2ndto 3rdmonth
Every 2-4 weeks – for the 4thto 6thmonth
Every 4-6 months – for the 6thto 12thmonth
Every 3-6 months after the first year of transplantation.
KTR: Patient access
The patients should have access to support services and results. Their information should be available to them in written and electronic formats.
KTR: Chronic transplant care review
A detailed review should be performed annually after the procedure, and it should be facilitated by a health care professional and it should address medical, social, psychological and sexual areas. The patients should have ready access to a renal dietician, social worker, pharmacist and psychologist.
KTR: Non-adherenceKTR: Recognizing non-adherence
Factors associated with non-adherence should be identified and a pathway should be in place for patients as at high-risk of non-adherence.
KTR: Immunosuppressive treatment KTR: Immunosuppressive regimen
The patient, the patient’s caregiver and the health care provider should engaged in the discussion process. Immunosuppressive therapy includes:
1. Induction immunosuppression
The medications begin before or at the time of the transplantation
The biological agent used for patients who have a low immunological risk is IL2-RA, and for those at higher risk may use T-cell depleting antibodies
CNI treatment is started at the time of transplantation
2. Maintenance immunosuppression
Consists of a CNI, an anti-proliferative agent (such as mycophenolate mofetil), with or without a corticosteroid
Mycophenolate mofetil and enteric coated mycophenoalte sodium have equivalent immunosuppression
The aim is to reach minimum target levels for CNIs by the third month after transplantation
The immunosuppression requires monitoring. Tacrolimus and ciclosporin levels should be initially monitored three times a week. This aids in dose adjustment and review during unexplained graft dysfunction.
The patients should not switch their medications for generic versions that have not been verified.
KTR: Acute rejection A transplant biopsy should be carried out without delay to diagnose acute rejection. Obtaining two cores, with a 16 guage biopsy needle will increase the sensitivity of the investigation.
For acute cellular rejection, high does intravenous corticosteroids are the first-line of treatment, progressing to maintenance doses. Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection.
For antibody mediated rejection (AMR), steroids, plasma exchange, intravenous immunoglobulin, anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib may be used.
The immunosuppression should be adjusted after an episode of acute rejection.
KTR: Chronic Allograft injury Early identification and diagnosis allows for a better prognosis of the graft. Serial monitoring of the patient’s serum creatinine, urine protein or albumin:creatinine ratio (ACR) should be performed. A renal biopsy is the investigation of choice to elicit the cause of the dysfunction. During this time, a serum sample should be taken to look for HLA-specific antibodies.
If the cause is CNI toxicity, the CNI should be withdrawn. Immunosuppression doses should be optimized if there is ongoing immune injury.
The indications of a renal biopsy include:
Persistent increase in serum creatinine which cannot be explained by another cause
Every 7-10 days during delayed graft function (DGF)
If expected renal function is not achieved within 4-8 weeks after transplantation
Sustained new onset proteinuria.
KTR: Cardiovascular disease and lifestyle The management of hypertension is crucial. The blood pressure should be regularly monitored and should be <140/90 mmHg in clinic.
Fasting lipid levels should be measured annually for KTR, and the treatment targets should be similar to those of the general population. The choice of medication should account for the concurrent immunosuppression medications.
Screening for the development of port-transplant diabetes mellitus (PTDM) should be done at each clinic visit. The diagnosis of PTDM is made once the patient has reached stable maintenance immunosuppression.
All KTR patients should receive the standard treatment for ischemic heart disease, including thrombolysis, revascularization and secondary prevention.
Patients receiving a renal transplantation should be encouraged to stop smoking.
Advice on a healthy lifestyle should be emphasized at every clinic visit. This includes a healthy diet, target ideal body weight, physical activity and reduced alcohol consumption.
KTR should be screened for breast, cervical, prostate, colon cancer. The patients should be aware of the malignancy risk. Non-melanoma skin cancer advice should be provided. Immunosuppression should be reduce if neoplasia develops. M-TORs have specific anti-tumor effects in Kaposi sarcoma.
KTR: Infection complicationsThe patients should be vaccinated with inactivated viruses and influenza annually. They should not receive live attenuated vaccines. Hepatitis B surface antibody levels should be checked annually, if the titres fall below 10 mIU/mL, the patient should be revaccinated. A pneumococcal vaccine booster should be provided every 5 years.
Prophylaxis for CMV should continue for 3-6 months, and treatment should be administered for 6 weeks after treatment with a TDA. The first line treatment for severe CMV infection is intravenous ganciclovir is used. For mild to moderate disease, oral valganciclovir can be used. The treatment duration should depend on the viral load.
EBV viral load should be monitored regularly, and immunosuppression should be reduced if EBV titres rise significantly.
Primary, uncomplicated or disseminated VZV infection should be treated with intravenous acyclovir or oral valaciclovir. Immunosuppression doses should be adjusted.
HSV systemic infection should be treated with intravenous acyclovir for at least 14 days and reduction in immunosuppression.
BK nephropathy should be screened when renal function deteriorates due to an unexplained reason. Urine microscopy should be used to screen for BK virus (BKV), and biopsy should be done to diagnose BKV. There is no definitive treatment, but immunosuppression should be reduced.
All patients with confirmed pneumocystis jirovecii infection (from respiratory secretions) should be treated for 14- 21 days with co-trimoxazole, or pentamidine. For patients with severe disease, consider additional glucocorticoid therapy.
For prophylaxis pf PJP, all patients should receive 3-6 months of co-trimoxaole treatment after the surgery, oral anti-fungal medication for a week and isoniazid with pyridoxine 6 months after transplantation.
All blood components should be for hepatitis E.
KTR: Bone and joint diseasePatients high at risk for osteoporosis should avoid the use of steroids. Severe hypoparathyroidism should be treated prior to the surgery. Hyperuricemia should be managed with colchicine, allopurinol should be avoided when using azathioprine. Reduced doses of CNIs should be considered in patients suffering from intractable bone pain caused by CNIs.
KTR: Hematological complicationsAnemia should be managed as per CKD patient guidelines. Polycythemia should be treated with angiotensin converting enzyme inhibitors or angiotensin receptor blockers, venesection in refractory cases. Hemoglobin should be monitored at every clinic visit.
KTR: Reproductive issues MPA-containing immunosuppressant medications and m-TORi should be stopped prior to conception and replaced appropriately. Conception should be attempted after at least one year of transplantation.
Counsellors and the obstetric teams should be involved. Aspirin 5mg daily from 12 weeks of gestation until the birth should be initiated to reduce the risk of pre-eclampsia.
Male patients should be counselled that m-TORi may reduce sperm count.
Summary of audit measures for the post-operative care of the kidney transplant recipient
Proportion of blood results available for review, and reviewed, within 24 hours
Proportion of units with a written follow-up schedule available to all staff and patients
Percentage of patients accessing their results through Renal Patient View
Percentage of total patients assessed in an annual review clinic
Recording “Did Not Attend” (DNA) rates for all patients
Recording sub-therapeutic drug levels. Measuring within-patient variability of CNI levels
Percentage of total patients receiving induction with ILRAs and TDAs
Percentage of de novo KTRs receiving tacrolimus
Percentage of de novo KTRs receiving MPA based immunosuppression
Percentage of de novo KTRs receiving corticosteroid maintenance therapy
Use of generic agents
Severity of biopsy proven acute rejection (BPAR) recorded by Banff criteria
Percentage of KTRs with BPAR in first 3 months and first 12 months
Percentage of KTRs requiring TDAs to treat rejection in first year
Complication rates after renal transplant biopsy
The percentage of KTRs with BPAR in first 3 months and the first 12 months
The percentage of KTRs with a donor specific HLA antibody at the time of biopsy
The percentage of KTRs with positive C4d staining on biopsy
Proportion of patients receiving a target blood pressure of 140/90 mmHg or 130/80 mmHg in the presence of proteinuria (PCR >100 mg/mmol or ACR >70 mg/mmol)
Proportion of patients with proteinuria assessed by dipstix and, if present, quantified at each clinic visit
Proportion of renal transplant recipients with an annual fasting lipid profile
Proportion of RTR taking statins (including the type of statin) for primary and secondary prevention of premature cardiovascular disease
Proportion of patients on other lipid lowering agents
Proportion of patients achieving dyslipidaemia targets
Incidence of post-transplant diabetes mellitus (PTDM) at three months and at annual intervals thereafter
Proportion of patients who require insulin, and in whom remedial action is undertaken – minimisation of steroids and switching of CNIs
The proportion of patients with PTDM enrolled in screening for extra-renal complications of PTDM
Proportion of patients with ischaemic heart disease
Proportion of patients suffering myocardial infarction
Proportion of patients undergoing primary revascularisation
Proportion of patients receiving secondary prevention with a statin, anti-platelet agents and renin angiotensin system (RAS) blockers
Proportion of KTRs who smoke
Proportion of cigarette smoking KTRs who have been given formal advice or offered help with cessation
Proportion of patients who are obese (BMI>30 kg/m2 )
Proportion of patients having screening procedures for neoplasia at the annual review clinic
Incidence of CMV disease
Rate of EBV infection and PTLD
Completeness of records for EBV donor and recipient serology
Rates of primary VZV and shingles infection
Completeness of records for VZV recipient serology
Rates and outcomes of HSV infections
Rates of BK viral infection in screening tests
Rates and outcomes of BK nephropathy
Frequency of bisphosphonate use
Incidence of fractures
Incidence of hyperparathyroidism
Incidence of parathyroidectomy
Use of cinacalcet
Frequency of hyperuricaemia and gout
Prevalence of anaemia
Prevalence of polycythaemia
Pregnancy rates and outcomes
Prevalence of sexual dysfunction
Rihab Elidrisi
2 years ago
1. Kidney Transplant Recipient (KTR):
The organisation of Outpatient Follow-up includes good clinic infrastructure ensuring the availability of health care professionals. Clinic frequency suggests that uncomplicated patients may be reviewed progressively in regular intervals. All patients should have access to support services and results. 2. Kidney Transplant Recipient: It is important to prevent, detect and take necessary action towards non-adherence in kidney transplant recipients. 3. Kidney Transplant Recipient: Immunosuppressive treatment · Induction immunosuppression therapy should take into account the following: Immunosuppressive drugs should be started before or at the time of renal transplantation. · Induction therapy with biological agents should be administered to all KTRs. In patients at low immunological risk, this will generally involve an interleukin-2 receptor antagonist (IL2-RA) and higher immunological risk may be considered for T-cell (lymphocyte) depleting antibodies (TDAs) · Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance. · CNI should be started at the time of transplantation and not delayed until the graft is functioning. · Maintenance immunosuppression should normally consist of a calcineurin inhibitor (CNI) and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs. · Mycophenolic acid-based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception. · KTRs who are unable to tolerate tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second-line agents such as ciclosporin, sirolimus, everolimus, or belatacept. · Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological-risk kidney transplant recipients.
if any signs of rejection, failure, opportunistic infection, need for graft biopsy, treatment (ABMR, cellular mediated), chronic rejection, allograft nephropathy if any progressive disease treats chronic kidney disease failure consequences accordingly.
Amit Sharma
2 years ago
Summarise this article
The article deals with guidelines for the care and follow-up of kidney transplant recipients (KTRs) post-operatively.
Guideline 1: A dedicated outpatient (OP) area with a consultant, having facilities for receiving blood reports within 24 hours and reviewing them within 24 hours should be available. The patients should be able to access services online and should be able to contact OP services via a single point of contact. The patient should be under close follow-up with graded gap in follow-up visits with time. The OP clinic should be patient-centric with presence of specialists involving multiple domains of patient care and should perform a detailed annual review.
Guideline 2: Patients more prone to non-adherence should be identified and managed pre-emptively.
Guideline 3: Patient and care-giver should be involved in selecting induction and maintenance immunosuppression.
Induction therapy should be started at time of transplantation. Low-risk patients can be induced with IL2 receptor antagonists while those with steroid sparing or CNI sparing regime as well as high-risk patients could be induced with T-cell depleting antibodies (TDAs).Maintenance immunosuppression should include a calcineurin inhibitor – CNI (preferably tacrolimus), which should be started at time of transplant, an anti-proliferative agent (mycophenolate – MPA preferred over azathioprine except in females planning to conceive), with or without (in low-risk patents) corticosteroids. Generics should be used only if their bioequivalence has been proved. CNI levels should be monitored regularly, especially when changing doses or formulation.
Guideline 4: A transplant kidney biopsy, 2 cores using a 16-gauge biopsy needle and staining with C4d and SV40, with DSA testing should be done before treating an acute rejection. Protocol biopsy should be done in persisting delayed graft function.
High dose intravenous corticosteroids should be given for acute cellular rejection (ACR), while refractory or aggressive vascular rejection will require TDAs. Antibody mediated rejection (AMR) will require one or more of steroids, plasma exchange, IVIG, anti-CD 20 antibody, TDAs or bortezomib. Post-rejection, azathioprine should be changed to MPA, dose of MPA should be maximized and steroids added if on steroid-free regimen.
Guideline 5: Early identification of graft injury can be done by monitoring of renal function (creatinine and proteinuria) on each follow-up visit. In presence of graft dysfunction or sustained new-onset proteinuria, a renal biopsy with DSA testing should be done. Treatment of graft dysfunction as per the etiology should be done (CNI withdrawal in case of CNI toxicity, and immunosuppression intensification in case of ongoing immune injury).
Guideline 6:BP should be measured on each follow-up visit and controlled using antihypertensives. Causes of resistant hypertension should be evaluated and treated. Annual lipid profile testing should be done and dyslipidemia should be treated, especially in those with cardiovascular risk using statins. Screening for post-transplant diabetes mellitus (PTDM) should be done at each follow-up visit and should be managed with consultation of endocrinologist. Regular screening for diabetic complications should be done. Ischemic heart disease should be managed as per standard protocols. Smoking cessation, maintaining a healthy lifestyle with regular physical activity, and maintaining weight should be encouraged.
Guideline 7: Patients should be made aware about risks of malignancies and screened for skin, cervical, breast, colon, and prostate cancer, Self-examination for detection of cancers should be taught. Skin examination by specialist should be done every 6 months for 5 years and then annually. For non-melanoma skin cancer (NMSC), patients should be taught above avoiding direct sunlight exposure and use of sunblock. If neoplasia develops, immunosuppression reduction with use of mTOR inhibitors in de novo malignancy is suggested (especially in Kaposi sarcoma).
Guideline 8: Vaccination with inactivated viruses should be done, including annual influenza vaccination, pneumococcal vaccine (every 5 years) and hepatitis B virus vaccination if anti HBsAb levels are low. Pre-transplant donor and recipient serology for CMV and EBV should be recorded. CMV prophylaxis should be given for 3-6 months post-transplant, and for 6 weeks after use of TDAs. CMV infection can be treated using oral valganciclovir or intravenous ganciclovir (in life-threatening disease). In presence of post-transplant lymphoproliferative disease (PTLD), immunosuppression should be reduced or stopped. EBV viral load should be monitored after treatment of rejection. Varicella zoster virus (VZV) infection treatment will require oral acyclovir or valaciclovir with immunosuppression reduction during infection. Herpes Simplex Virus (HSV) infection should be treated with oral or intravenous acyclovir with reduction of immunosuppression during infection, with prophylaxis in case of recurrent infections. BK virus nephropathy screening using urine examination and PCR on serum/ urine should be done in case of unexplained graft dysfunction, and can be confirmed by a kidney biopsy. Treatment requires reduction in immunosuppression. Pneumocystis jirovecii prophylaxis with co-trimoxazole for 3-6 months post-transplant should be given. Confirmed infection should be treated with oral or intravenous co-trimoxazole (if contra-indicated, use pentamidine) for 14-21 days, with adjunctive glucocorticoids in severe disease. Oral antifungal prophylaxis should be given for 1 week post-transplant, and in latent TB INH with pyridoxine for 6 months should be given.
Guideline 9: KTRs with or at high risk of osteoporosis should be screened with DEXA scan, and considered for steroid-avoiding regimen. Osteoporosis should be treated as per guidelines. Severe hyperparathyroidism should be treated pre-transplant and cinacalcet can be used in KTRs. Gout in KTR can be treated using colchicine and brief course of oral prednisolone in case of acute gout. NSAIDs should be avoided. Febuxostat and allopurinol should not be used with azathioprine. In intractable bone pains, CNI reduction or withdrawal and dihydropyridine calcium channel blocker use should be considered.
Guideline 10: Anemia should be treated as per management of anemia in CKD. Polycythemia should be treated (if hematocrit is >52% in men and >49% in women) using ACEi or ARBs and venesection in refractory cases.
Guideline 11: Before attempting conception, KTRs should have a stable graft function for 1 year after transplant and MPA as well as mTOR inhibitors should be replaced. Pre-transplant and post-transplant counselling regarding fertility and contraception should be provided to both the female KTRs and their partner. Pregnancy should be managed with multidisciplinary approach. Aspirin should be started from 12weeks of gestation till delivery, if not contraindicated. Breastfeeding risks and benefits should be discussed with the KTR. Male KTRs should be explained about theoretical teratogenic risk with MPA and reduced sperm counts with mTOR inhibitor use (hence to be avoided in patients wishing to maintain fertility or replace prior to conception). Sexual dysfunction should be enquired into and managed. Sildenafil can be used if KTR is not on nitrates.
2. What is the evidence provided by this article?
The level of evidence is level 5 – guidelines
Mohammad Alshaikh
2 years ago
Summarise this article Introduction: after kidney transplantation the post operative care of the recipient is mandatory, this article figure out the guide line in patient care, prevention of acute rejection, optimization of graft function and prevention of opportunistic infection, preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression – malignancy, infection and premature cardiovascular disease. Kidney Transplant Recipient (KTR): Organisation of Outpatient Follow-up: – The recipient should be reviewed in a dedicated outpatient area, by a consultant level health care professional (2D). – The blood test result should be available within 24 hours (2D). – There should be access to a multidisciplinary renal team including pharmacist, dietician, social worker and psychologist (2D). – Clinic visit frequency (2C): · 2-3 times weekly for the first month after transplantation. · 1-2 times weekly for months 2-3. · Every 2-4 weeks for months 4-6. · Every 4-6 weeks for months 6-12. · 3-6 monthly thereafter. – Patient access (2C): · Open access to the renal transplant outpatient service with ease of contact for enquiries · Patient information should be available in both written and electronic formats. – Chronic transplant care review(2C): Annual patient review, patient centered clinic with concerns in medical, social, psychological and sexual domains, and an Access to a renal dietician, social worker, specialist renal pharmacist and/or psychologist should be readily available from this clinic. Kidney Transplant Recipient: Non-adherence (2C): · Factors associated with non-adherence should be identified. · An established interventional pathway should be in place for those at high risk of or with proven nonadherence. · Pathways should be in place for paediatric KTRs in transition and for adolescent KTRs. Immunosuppression regimen
patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression.
Induction immunosuppression
Immunosuppressive drugs should be started before or at the time of renal transplantation.
Induction therapy with biological agents should be administered to all KTRs. In patients at low immunological risk, this will generally involve an interleukin-2 receptor antagonist (IL2-RA). Recipients at higher immunological risk may be considered for T-cell-depleting antibodies.
Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance.
CNI should be started at the time of transplantation and not delayed until the graft is functioning.
KTR: Maintenance immunosuppression
maintenance immunosuppression should normally consist of a calcineurin inhibitor and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs.
low-medium dose tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice in patients also taking steroids who are low and medium immunological risk and are not at high risk of developing post transplant diabetes mellitus.
mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception.
slow release tacrolimus may be used as an option as second line agents for patients who suffer intolerable side effects related to peak dose toxicity.
KTRs who are unable to tolerate tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second-line agents such as ciclosporin, sirolimus, everolimus, or belatacept.
MPA-based drugs should be the first-line antiproliferative agent, in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception.
mycophenolate mofetil and enteric-coated mycophenolate sodium provide equivalent maintenance immunosuppression.
steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients.
aiming for minimum target levels for CNIs in uncomplicated renal transplantation after 3 months.
CNIs should not be withdrawn.
t if steroids are not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less).
long-term monitoring of immunosuppression levels is required as follows:
Tacrolimus and ciclosporin levels should be monitored. The initial frequency should be three times a week. Levels should also be checked when any medication with possible interactions is prescribed, the dosage is changed, the formulation is changed, or when there is unexplained graft dysfunction.
Tacrolimus should be monitored by the trough (C0) level, while ciclosporin can be monitored by either C0 or 2- hour post dose (C2).
Tacrolimus and ciclosporin levels should be available within 24 hours of taking blood samples in the first three months after transplantation.
The utility of monitoring mycophenolic acid (MPA) C0 levels is uncertain.
Sirolimus should be monitored by the C0 trough level.
Prescribing and the use of generic agents
generic immunosuppression compounds should not be used unless they have been shown to be bioequivalent and approved by the European Agency for the Evaluation of Medicinal Products.
KTRs should be made aware of the existence of generics and the importance of not switching between preparations without appropriate supervision.
drugs should be prescribed by brand name.
KTRs should be closely monitored after switching between generic preparations until a new steady state is established.
Diagnosis of acute rejection
a transplant renal biopsy should be carried out before treating an acute rejection episode unless this will substantially delay treatment or pose a significant risk to the patient.
two cores of renal tissue should be obtained at transplant biopsy since this will increase the sensitivity of the investigation.
a 16 gauge automated core biopsy needle is used where possible to provide the best compromise between diagnostic usefulness and patient tolerance of the procedure.
a protocol transplant renal biopsy, defined as a biopsy performed in a stable graft without clinical evidence of acute rejection, be considered in the setting of persisting delayed graft function.
routine C4d and SV40 staining should be performed upon transplant biopsies to address other causes of graft dysfunction.
a serum sample be sent at the time of renal biopsy (for graft dysfunction) to look for HLA-specific antibodies.
Treatment of acute rejection
borderline acute cellular rejection should be treated in the context of acute graft dysfunction.
high dose intravenous corticosteroids should be the first line treatment for acute cellular rejection.
maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type.
lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III).
antibody mediated rejection should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib.
BTS guidelines on antibody incompatible transplantation for management of rejection in the context of antibody incompatible transplantation.
after an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximized.
Diagnosis of Chronic Allograft Injury
early identification of graft injury is desirable to maximize the potential for intervention. A proactive and systematic approach should have employed to manage graft dysfunction.
Detection of Chronic Allograft Injury
renal function should be monitored at each clinic visit by assessment of serum creatinine and qualitative evaluation of urine protein excretion by dipstick, supplemented by spot protein:creatinine ratio or albumin:creatinine ratio if positive.
Diagnosis of Chronic Allograft Injury
renal biopsy is the optimal investigation for parenchymal causes of graft dysfunction where the cause is uncertain.
renal biopsies in patients with chronically deteriorating function should be stained for C4d and SV40.
a serum sample should be sent at the time of renal biopsy (for graft dysfunction) to look for HLA-specific antibodies.
Treatment of chronic allograft injury
By withdrawal of calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy.
By intensification of immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection).
In a similar fashion to other patients with chronic kidney disease (CKD), following similar preventative strategies and with timely referral to low clearance services.
Renal biopsy in chronic allograft injury
If there is a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy-proven acute rejection.
Every 7-10 days during delayed graft function.
If expected renal function is not achieved within 4-8 weeks.
If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol).
Hypertension
Blood pressure should be recorded at each clinic visit.
Clinic blood pressure should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35).
Home blood pressure recordings and 24-hour ambulatory recordings may be helpful in some instances but lower BP targets should then be set (home and or ambulatory daytime measures <135/80mmHg).
There is no evidence that any antihypertensive agent is better than any other and effort should be focused on achieving absolute blood pressure control rather than the use of individual agents.
Inhibitors of the renin-angiotensin system may be more effective in the minimization of proteinuria but should be used with caution in the first 3 months post-transplant.
Resistant hypertension may be due to transplant renal artery stenosis and should be investigated according to local practice.
Dyslipidemia
Fasting lipid levels should be measured on an annual basis in renal transplant recipients.
Treatment targets should be the same as in the general population.
KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease.
The choice and dose of statin should take into account concurrent immunosuppression. High-dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/or calcium channel antagonists.
Diabetes mellitus
Screening for the development of post-transplant diabetes mellitus (PTDM) by dipstick urinalysis and measurement of blood sugar level at each clinic visit.
Post-transplant immunosuppression should take into account risk factors for the development of diabetes.
The diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing.
A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression.
Post-transplant diabetes should be managed in collaboration with specialists in diabetic medicine.
All units should have a protocol for the management of post-transplant diabetes.
KTR with diabetes (either prior to transplantation or PTDM) should undergo screening for diabetic complications (retinal screening, foot care, neuropathy) in line with guidelines for non-KTR patients with diabetes.
Ischemic heart disease
KTRs receive standard treatment for ischemic heart disease, including thrombolysis, revascularization, and secondary prevention.
Smoking cessation
smoking should be strongly discouraged in transplant recipients.
Lifestyle measures
Maintenance of a healthy diet should be encouraged.
An ideal weight should be targeted (body mass index (BMI) ≤25 kg/m2 ).
Weight management services should be available.
We suggest that KTRs participate in physical activity at a level similar to that recommended to age and comorbidity-matched counterparts from the general population.
Alcohol consumption should be within national guidelines.
Recreational drug use should be avoided.
The use of over-the-counter medications (without discussion with clinical staff) and non-proprietary medications (e.g. herbal medicines) should be discouraged.
Screening for cancer
Screening should be similar to the general population for cervical, breast, colon and prostate cancer.
Screening is not recommended for renal cell carcinoma.
Patient education pre and post-transplantation.
Patients should be aware of malignancy risk and encouraged to report symptoms which may represent de novo malignancy (e.g. breast or testicular lumps).
· Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant.
Patients with cirrhosis should undergo an annual hepatic ultrasound and determination of serum alpha-fetoprotein.
Non-melanoma skin cancer
KTRs should be educated about the adverse effects of sun exposure.
an individualised assessment of hazards should be made according to risk factors.
patients should be encouraged to cover their skin in direct sunlight and to use total sunblock (Sun Protection Factor ≥50).
self-examination should be encouraged with guidance provided. This should be supplemented by at least a biannual review by a trained healthcare professional up to 5 years post-transplant and an annual review from 5 years.
the prescription of acitretin as chemoprophylaxis be considered in those with ≥2 previous NMSC if there are no contraindications.
Immunosuppression in cancers
immunosuppression should be reduced if neoplasia develops.
(m-TORi) are considered as alternative immunosuppressive agents in KTRs who develop de novo malignancy.
Vaccination
Should be vaccinated with inactivated viruses as per the normal population.
Should receive annual influenza vaccination unless contraindicated.
Should have hepatitis B surface antibody (HBsAb) levels rechecked annually and be revaccinated if antibody titers fall below 10 mIU/mL.
Should not receive live attenuated vaccines.
Should receive the pneumococcal vaccine and a booster every five years.
Prophylaxis and treatment of CMV disease
Prophylaxis should be continued for 3-6 months, until immunosuppression has been reduced to long-term maintenance level.
Treatment should be administered for 6 weeks after treatment with a TDA.
All transplant units should be able to measure CMV serological status and quantify viral load.
Donor and recipient CMV status should be recorded at the time of transplantation.
Each unit should have a written protocolised CMV strategy based on prophylaxis or pre-emptive therapy.
For the treatment of mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are of equivalent efficacy.
The first line treatment of for life-threatening CMV disease is intravenous ganciclovir.
Treatment duration should be determined by monitoring viral load.
EBV infection
immunosuppression should be reduced or stopped following the development of post-transplant lymphoproliferative disease.
Both donor and recipient should have their EBV serology recorded at the time of transplantation.
All high-risk (D+ /R- ) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year.
EBV viral load should be monitored after the treatment of rejection.
Total immunosuppression should be reduced when EBV titers rise significantly.
VZV infection
Primary infection (chickenpox) should be treated with intravenous acyclovir or oral Val acyclovir until the lesions scab over.
Uncomplicated shingles should be treated with oral acyclovir or Valacyclovir until the lesions scab over.
Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with intravenous acyclovir until the lesions scab over, together with a reduction in immunosuppression.
Varicella-susceptible KTRs (i.e. VZV IgG negative) with primary exposure to VZV should receive intravenous immunoglobulin, ideally within 96 hours, but up to a maximum of 10 days following exposure. If unavailable or after 10 days, oral acyclovir should be prescribed for seven days.
Patients on the waiting list who are VZV IgG negative should be vaccinated prior to transplantation.
Immunosuppression should be reduced during primary infection.
HSV infection
Superficial HSV infection should be treated with appropriate oral agents until the lesions have resolved.
Systemic HSV infections should be treated with intravenous acyclovir and a reduction in immunosuppression until a response occurs, and oral medication should be continued for at least 14 days.
KTRs suffering frequent recurrent HSV infections should consider oral prophylaxis.
BK nephropathy
confirmed BK nephropathy should be treated by reduction in immunosuppression.
Screening should also be carried out when renal function deteriorates in an unexplained fashion.
KTRs should be screened for BKV viral load by performing urine microscopy for decoy cells or by polymerase chain reaction (PCR) on urine or serum.
Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40. Two cores containing medullary tissue should ideally be examined.
Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml.
There is no established specific treatment for BK nephropathy.
Re-transplantation can safely be considered in patients who have BK nephropathy diagnosed in an earlier graft.
Pneumocystis jirovecii infection – treatment and prophylaxis
All patients with confirmation (microscopy or PCR) of Pneumocystis jirovecii in respiratory secretions should be treated for 14 to 21 days with co-trimoxazole orally or intravenously (15-20mg/kg in three or four divided doses).
Patients with contraindications to treatment with co-trimoxazole should receive pentamidine (4mg/kg/day intravenously).
Adjunctive glucocorticoid therapy may be considered in patients with severe disease.
All patients should receive 3-6 months of treatment with co-trimoxazole 480mg daily for Pneumocystis jirovecii prophylaxis following renal transplantation.
Post-transplant infection prophylaxis
All patients should receive 3-6 months of treatment with co-trimoxazole 480 mg daily.
Oral antifungal prophylaxis should be administered for one week after transplantation.
In selected patients, prophylaxis against mycobacterium tuberculosis with daily isoniazid (supplemented with pyridoxine) should be instituted for six months after transplantation.
Hepatitis E Virus
Hepatitis E Virus (HEV)-screened blood components should be given to all KTR.
Osteoporosis
KTRs suffering from osteoporosis or at high potential risk should be considered for steroid-avoiding immunosuppression.
KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2.
Treatment should be according to the Royal College of Physicians (RCP) guidelines for steroid-induced osteoporosis.
Tertiary hyperparathyroidism
Severe hyperparathyroidism should be treated prior to transplantation.
Cinacalcet can be used in KTR.
Treatment should be the same as for other patients with CKD.
Treatment of gout
Allopurinol and febuxostat should be administered with azathioprine.
Hyperuricemia should be treated when associated with gout, tophi or uric acid stones.
Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided in KTRs.
Acute gout may be treated with brief a course of oral prednisolone.
Colchicine is an effective treatment for gout in KTR.
Calcineurin inhibitor bone pain
Reduction or withdrawal of CNIs should be considered in KTRs with intractable bone pain.
Dihydropyridine calcium antagonists also may be beneficial.
Anaemia
chronic anaemia should be managed in the same way as other patients with CKD.
Polycythaemia
initial treatment should be with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
Haemoglobin levels should be monitored at every clinic visit.
Treatment should be initiated if the haematocrit or packed cell volume exceeds 52% in men and 49% in women.
Venesection may be used in refractory cases.
Conception and contraception
MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately.
KTRs should wait for one year after transplant and have stable function before attempting conception.
Counselling regarding fertility and reproduction should be offered to female KTRs and their partners either prior to transplantation or soon afterwards.
m-TORi should be stopped prior to conception and replaced as appropriate.
Pregnancy should be jointly managed with an Obstetrics department with experience of care of KTR.
KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth of the baby unless there are contraindications.
The risks and benefits of breastfeeding should be discussed.
Contraception advice should be similar to the general population.
Male KTRs are advised that MPA containing have theoretical teratogenic potential in men taking these agents.
KTRs should be advised that m-TORi reduce the male sperm count and counselled accordingly.
All immunosuppressive drugs other than m-TORi can be used in male KTRs.
The decision to continue MPA containing compounds in a male KTR wishing to conceive should balance the risk of theoretical teratogenicity against the risk of rejection on changing from MPA to azathioprine.
Men on m-TORi who wish to conceive should discontinue these agents prior to conception and replace them as appropriate.
Men who wish to maintain fertility should avoid m-TORi or bank sperm prior to starting these drugs.
Sexual dysfunction
Specific enquiries should be made regarding sexual dysfunction, preferably at an annual review clinic.
Care pathways for dealing with sexual dysfunction should be established.
Close liaison with local andrology service is recommended.
Sildenafil is safe and effective in male KTR not taking nitrates
What is the evidence provided by this article? Level of evidence I – guidelines
Manal Malik
2 years ago
Post-Operative Care in the Kidney Transplant Recipient (BTS GUIDELINES- 2017)Introduction:
These guidelines for the period post renal transplantation the management of kidney transplantation divided into two phases:
1. An early post-operative phase when prevention of acute rejection, optimization of graft function and prevention of appropriate infection
2. Late phase to preserve good graft function after transplantation
Summary of clinical practice guidelines:
· KTR clinic infrastructure constant level after result of blood test should be variable within 24 hours
· Access to multi- disciplinary renal team including pharmacist, dietician, social worker and psychiatrist
· Clinic frequency
· 2-3 weekly for the first month after transplantation
· 1-2 time weekly for 2 to 3 months
· Every 2-4 weeks for 4-6 months
· 4-6 week for 6-12 months
· KTR patient should have a single result renal transplant service and ==information should available both written and electronic
· Chronic transplant care review
· KTR recognizing ban-Adherence should identified factors for non-adherence and interventional pathway for high-risk transplant recipient
Kidney transplant recipient: immunosuppressive treatment
Patients should be engaged in the dissection around selection of indication agent and maintenance immunosuppression
Induction therapy:
Interleukin-2 receptor antagonist for low immunological risk recipient
T-cell lymphocyte depleting antibodies for higher immunological risk.
KTR induction immunosuppressive
CNI should be started at the time of transplantation (2c)
Maintenance immunosuppression in KTR consist of CNI, antiproliferative agent with or without corticosteroid in low and reducing immunological risk KTRs
Tacrolimus trough level 4-8 ng/ml in low and medication
Immunological risk are not at risk of develop PTD(2c)
Mycophenolate acid-based regimen be the first anti-==performance to Azathioprine except futile KTRs are unwilling to use contraception(2B)
Slow-release TAC second line for whom had side effects to peak dose toxicity(2C)
KTRs who are unable to tolerate tacrolimus or who suffer a serious adverse reactions to it is use to be considered second-line agents such as ciclosporin sirolimus, everolimus (B1)
Steroid avoidance or withdrawal can be used during the first week after transplantation in low immunological-risk kidney transplant recipients (2B)
Minimum target levels for CNI in uncomplicated renal transplantation after 3 months (2c)
Steroid unknown regimen should be a low dose (prednisolone 5mg per day or less) (2c)
Maintain of TAC and cyclosporin if:
· Medication interaction
· Dosage change
· Unexplored graft function (2c)
· Mycophenolic acid co level uncertain (2D)
· Sirolimus should be monitored by the co trough level(2c)
· Immunosuppression drug should be prescribed by brand name (2D)
A transplant kidney biopsy should be carried out before treating acute rejection episodes(1C).
Recommended high-dose corticosteroids should be the first-line treatment for acute cellular rejection(1D).
Restarted steroid in steroid-free patients with an acute rejection of any type (2D).
Suggest that lymphocyte-depleted agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection B or T 4 type II or type III (2 C).
We suggest that antibody-mediated rejection (AMR) should be treated with one or more of the following medications: steroids, plasma exchange, and intravenous immunoglobulin.
Anti-CD 20 antibodies, lymphocyte-depleting antibodies or bortezomib (2C).
After an episode of rejection (unless associated with lower CNI levels)
Azathioprine should be switched to MPA-based immunosuppression, MPA should be started or the existing dose of MPA maximized(2D)
We suggest that renal biopsy patients with critical deterioration function should be stained for C4d and SV40(2C).
Chronic allograft type should be treated by the withdrawal of calcineurin inhibitor if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy(2C)
Intensification of immunosuppression if there is evidence of ongoing immune injury.
Treat as CKD
Indication of kidney transplantation renal biopsy in chronic allograft injury:
Sustained new onset proteinuria develops PCR > 50/mg/mmol, an ACR>35mg/mmol (2 C)
If expected renal function is not achieved within 4-8 weeks(2D)
Every 7-10 days during delayed graft function (2C)
Persistent unexplained elevation of creatinine or failure to return to the baseline after an episode of biopsy prevents acute rejection BPAR (1C)
Hypertension:
BP clinically should be <140/90 mmHg.
Renin-angiotensin system may be more effective in the minimization of proteinuria but should be used with caution in the first 3 months post-transplant (2C).
The choice and dose of start in kidney transplantation dyslipidaemia should take into account immunosuppression high dose ≥ 40 mg sampling should be avoided combination with cyclosporin and calcium channel antagonist (2D).
The diagnosis of PTDM is made based WHO criteria for the diagnosis of DM.
The treatment target of dyslipidaemia in kidney transplantation should be the same in the general population (2C)
The diagnosis of DM is based on fasting or random blood, serum HA1c or oral GTT(1c).
Screening for cancer in kidney transplant patients should be similar to the general population for cervical, breast, colon and prostate cancer.
Kidney transplant patients with non-melanoma skin cancer.
C1: colchicine can be used for gout in kidney transplant patients (2D)
Kidney transplant patients recommended that MPA continuing immunosuppression drugs should be stopped prior to conception and replaced appropriately (1 A)
Kidney transplantation recognizing non-adherence is important to prevent and detect non-adherence in kidney transplant recipients (2C).
Kidney transplantation induction immunosuppression:
CNI should be started at the time of transplantation and not delayed until the graft is functioning (2C).
Maintenance immunosuppression kidney transplantation suggests avoiding steroid withdrawal during the first week after transplantation (2B).
Kidney transplantation: mainly if tacrolimus and cyclosporine levels should be maintained. TAC is co trough level and cyclosporin co or C2 is the post dose C2
Kidney transplantation vaccination should not receive live attenuated vaccines (2C).
Prophylaxis should continue for 3-6 months (1B)
Treatment should be given for 6 weeks after treatment with a TDA (1C).
In kidney transplantation: EBV we recommended that immunosuppression should be reduced or stopped following the development of post-transplant==
Kidney transplantation and infection:
Disseminated, ocular or invasive shingles should be treated with intravenous acyclovir until the lesion is scaly covered with a reduction in immunosuppression (1B)
Kidney transplantation: B/L nephropathy should be treated by reduction in immunosuppression(1D).
Kidney transplantation: pneumocystis juroveci infection prophylaxis should be for 3-6 months of treatment with co-trimoxazole 480 mg daily for pneumocystis jureveci prophylaxis following renal transplantation (1B).
Kidney transplantation for osteoporosis on long-term steroids or at high risk for osteoporosis should undergo Dexa-Scanning if GFR >30 ml/min/1.73m2 (2D).
Tertiary hyperparathyroidism should be treated before transplantation (2D)
Cinacalcet can be used in kidney transplantation (2C)
Kidney transplantation treatment of giant. We recommended that neither allopurinol nor febuxostat should with azathioprine (1c)
A transplant kidney biopsy should be carried out before treating acute rejection episodes(1C).
Recommended high-dose corticosteroids should be the first-line treatment for acute cellular rejection(1D).
Restarted steroid in steroid-free patients with an acute rejection of any type (2D).
Suggest that lymphocyte-depleted agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection B or T 4 type II or type III (2 C).
We suggest that antibody-mediated rejection (AMR) should be treated with one or more of the following medications: steroids, plasma exchange, and intravenous immunoglobulin.
Anti-CD 20 antibodies, lymphocyte-depleting antibodies or bortezomib (2C).
After an episode of rejection (unless associated with lower CNI levels)
Azathioprine should be switched to MPA-based immunosuppression, MPA should be started or the existing dose of MPA maximized(2D)
We suggest that renal biopsy patients with critical deterioration function should be stained for C4d and SV40(2C).
Chronic allograft type should be treated by the withdrawal of calcineurin inhibitor if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy(2C)
Intensification of immunosuppression if there is evidence of on going immune injury.
Treat as CKD
Indication of kidney transplantation renal biopsy in chronic allograft injury:
Sustained new onset proteinuria develops PCR > 50/mg/mmol, an ACR>35mg/mmol (2 C)
If expected renal function is not achieved within 4-8 weeks(2D)
Every 7-10 days during delayed graft function (2C)
Persistent unexplained elevation of creatinine or failure to return to the baseline after an episode of biopsy prevents acute rejection BPAR (1C)
Hypertension:
BP clinically should be <140/90 mmHg.
Renin-angiotensin system may be more effective in the minimization of proteinuria but should be used with caution in the first 3 months post-transplant (2C).
The choice and dose of start in kidney transplantation dyslipidaemia should take into account immunosuppression high dose ≥ 40 mg sampling should be avoided combination with cyclosporin and calcium channel antagonist (2D).
The diagnosis of PTDM is made based WHO criteria for the diagnosis of DM.
The treatment target of dyslipidaemia in kidney transplantation should be the same in the general population (2C)
The diagnosis of DM is based on fasting or random blood, serum HA1c or oral GTT(1c).
Screening for cancer in kidney transplant patients should be similar to the general population for cervical, breast, colon and prostate cancer.
Kidney transplant patients with non-melanoma skin cancer.
C1: colchicine can be used for gout in kidney transplant patients (2D)
Kidney transplant patients recommended that MPA continuing immunosuppression drugs should be stopped prior to conception and replaced appropriately (1 A)
Kidney transplantation recognizing non-adherence is important to prevent and detect non-adherence in kidney transplant recipients (2C).
Kidney transplantation induction immunosuppression:
CNI should be started at the time of transplantation and not delayed until the graft is functioning (2C).
Maintenance immunosuppression kidney transplantation suggests avoiding steroid withdrawal during the first week after transplantation (2B).
Kidney transplantation: mainly if tacromulus and cyclosporine levels should be maintained. TAC is co trough level and cyclosporin co or C2 is the post-dose C2
Kidney transplantation vaccination should not receive live attenuated vaccines (2C).
Prophylaxis should continue for 3-6 months (1B)
Treatment should be given for 6 weeks after treatment with a TDA (1C).
In kidney transplantation: EBV we recommended that immunosuppression should be reduced or stopped following the development of post-transplant==
Kidney transplantation and infection:
Disseminated, ocular or invasive shingles should be treated with intravenous acyclovir until the lesion is scaly covered with a reduction in immunosuppression (1B)
Kidney transplantation: B/L nephropathy should be treated by a reduction in immunosuppression(1D).
Kidney transplantation: pneumocystis juroveci infection prophylaxis should be for 3-6 months of treatment with co-trimoxazole 480 mg daily for pneumocystis jureveci prophylaxis following renal transplantation (1B).
Kidney transplantation for osteoporosis on long-term steroids or at high risk for osteoporosis should undergo Dexa-Scanning if GFR >30 ml/min/1.73m2 (2D).
Tertiary hyperparathyroidism should be treated before transplantation (2D)
Cinacalcet can be used in kidney transplantation (2C)
Kidney transplantation treatment of giant. We recommended that neither allopurinol nor febuxostat should be with azathioprine (1c)
evidence level 5
Mohamad Habli
2 years ago
Post-Operative Care in the Kidney Transplant Recipient Introduction
KTR management is broken into two phases:
A. an early post-operative phase to prevent acute rejection, optimize graft performance, and prevent opportunistic infection
1. Preventing acute rejection, optimizing graft function, and preventing opportunistic infection in the early post-operative phase
2. Preserving good graft function, ensuring medication adherence, and preventing immunosuppression’s long-term effects of malignancy, infection, and premature cardiovascular disease in the later phase
Summary of Clinical Practice Guidelines for Kidney Transplant Recipient Post-Operative Care
Kidney Transplant Recipient (KTR): Outpatient Follow-up Organization
KTR: Clinic infrastructure · Consultants should cover every transplant clinic · KTRs should be assessed in a dedicated outpatient area · Blood test results should be available within 24 hours · A multidisciplinary renal team should include a pharmacist, dietitian, social worker, and psychologist.
KTR: Clinic frequency simple individuals may be evaluated progressively less frequently (2C)
2-3 times a week during the first month after transplantation, then 1-2 times a week. 2-3 weeks per month for months 4-6 weeks per month for months 3-6 monthly after 6-12
KTR: All patients should have access to results and support services. (2C)
KTR: Annual post-operative chronic transplant care review (2C)
Non-adherence in kidney transplant recipients
KTR: Kidney transplant recipients must be monitored for non-adherence. (2C)
3. Kidney Transplant Recipient: Immunosuppressive therapy
The patient and caregiver should choose the induction agent and immunosuppressive maintenance (1D)
KTR: Induction immunosuppression
All KTRs should receive induction therapy with biological agents and immunosuppressive medications before or during kidney transplantation (1B).
1) an interleukin-2 receptor antagonist (IL2-RA) for low immunological risk people.
2) Higher immunological risk T-cell (lymphocyte) depleting antibodies (TDAs).
Lower immunological risk patients who want to avoid steroids or calcineurin inhibitors (CNIs) may benefit from TDA induction therapy. (1C)
KTR: Induction immunosuppression
· A CNI should be started immediately after transplantation, not after the graft is functional (2C)
KTR: Immunosuppression maintenance
· should normally consist of a CNI and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs (1B). In patients taking steroids who are low and medium immunological risk and not at high risk of post transplant diabetes mellitus (PTDM), tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice (2C)
Mycophenolic acid-based medications should be the first-line anti-proliferative treatment instead of azathioprine, except in fertile KTRs who refuse contraception. (2B
If peak dosage toxicity adverse effects are unacceptable, slow-release tacrolimus may be a second-line treatment (2C)
· the use of second-line medications such ciclosporin, sirolimus, everolimus, or belatacept if tacrolimus was not tolerated · MPA-based therapies should be the first-line antiproliferative agent, in preference to azathioprine, except in fertile KTRs who are unwilling to utilize reliable contraception (2B)
MMF and enteric-coated mycophenolate sodium provide comparable maintenance immunosuppression (2B)
In low immunological risk kidney transplant recipients, steroid avoidance or withdrawal might be employed during the first week after transplantation (2B)
· minimal target levels for CNIs in uncomplicated renal transplantation after 3 months · CNIs should not be removed (2B) · if steroids are not withdrawn during the first month, then they should be kept at low dose (prednisolone 5 mg per day or less) (2C)
KTR: Immunosuppression monitoring Tacrolimus and ciclosporin levels should be tested three times a week initially, and if: 1) a new medicine is administered 2) 2) the composition or dosage is altered
3) unexplained graft malfunction · Tacrolimus and ciclosporin levels should be provided within 24 hours of blood samples in the first three months after transplantation · Sirolimus should be monitored by the C0 trough level
4. Kidney Transplant Recipient: Acute rejection
KTR: Diagnosis of acute rejection · a transplant renal biopsy should be done before treating an acute rejection episode unless this will delay treatment or pose a significant risk to the patient · two cores of renal tissue should be obtained at transplant biopsy · a 16-gauge automated core biopsy needle is recommended · a protocol transplant renal biopsy is recommended for persisting delayed graft function · routine C4d and C4dx should be done
KTR: Treatment of acute rejection · high-dose intravenous corticosteroids should be the first-line treatment for acute cellular rejection · maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type · lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e., Banff category 4 Type II and III) · AMR should be treated steroids; plasma exchange; IVIG; anti-CD20 antibody, lymphocyte-depleting antibody, or bortezomib · following an episode of rejection (unless linked with low CNI levels) – switch to MPA-based immunosuppression, start MPA, or increase MPA dose.
5. Kidney Transplant Recipient: Chronic Allograft Injury · C4d and SV40 should be stained on renal biopsies in individuals with continuously decreasing function.
KTR: Treatment of chronic allograft injury · By withdrawing calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy · By intensifying immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection) · In a manner similar to other patients with chronic kidney disease (CKD), following similar preventative strategies and wit
KTR: Renal biopsy in chronic allograft damage. Indicated if: · a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection · every 7-10 days during delayed graft function (DGF) · if expected renal function is not achieved within 4-8 weeks · if sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol)
6. Kidney Transplant Recipient: Cardiovascular Disease and Lifestyle KTR: Hypertension · Blood pressure should be measured at each clinic appointment and should be <140/90 mmHg in clinic · There is no evidence that any antihypertensive drug is better than another · RAS inhibitors may be more successful in treating proteinuria · Resistant hypertension may be caused to transplant renal artery stenosis and should be examined.
KTR: Dyslipidaemia · Fasting lipid levels should be measured annually and treated as in the general population · KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease · High-dose simvastatin (>40mg daily) should be avoided in conjunction with ciclosporin and/or calcium channel antagonists
Diabetes mellitus
Dipstick urinalysis and blood sugar measurement at each clinic visit to screen for post-transplant DM (PTDM) Consider WHO criteria for DM diagnosis based on fasting or random blood, serum HBA1c, or OGTT · Once steady maintenance immunosuppression is established, PTDM can be diagnosed and managed with a diabetologist. Diabetic problems in KTR should be screened.
KTR: Ischemic heart disease · KTRs can receive typical ischaemic heart disease treatment, including thrombolysis, revascularization, and secondary prevention · transplant recipients should not smoke
KTR: Lifestyle measures · a healthy diet and body mass index (BMI) < 25 kg/m2 · limited alcohol intake and avoidance of recreational drug use · discourage the use of over-the-counter pharmaceuticals and herbal treatments.
7. Kidney Transplant Recipient: Neoplasia · Screening should be similar to the general population for cervical, breast, colon, and prostate cancer and not recommended for renal cell carcinoma · Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant · Patients with cirrhosis should undergo an annual hepatic ultrasound and determination of serum alpha fetoprotein · KTRs should be taught about the harmful effects of sun exposure and advised to cover their skin in direct sunlight and wear total sunbloc · self-examination should be encouraged with advice, at least biannual review by an up to 5 years post-transplant and annual review from 5 years · Acitretin may be used as chemoprophylaxis for patients with two or more non-melanoma skin cancers. m-TORi should be considered if neoplasia develops. m-TORs inhibit Kaposi sarcoma tumors.
Kidney Transplant Recipient: Infection Issues
KTR: Vaccination · KTRs should be vaccinated with inactivated viruses as per the normal population and receive annual influenza vaccination unless contraindicated · KTRs should have their HBsAb levels rechecked annually and be revaccinated if antibody titres fall below 10 mIU/mL · KTRs should not receive live attenuated vaccines Pneumococcal vaccine and boosters should be given to KTRs every five years.
KTR: Cytomegalovirus (CMV) illness
After TDA treatment, prophylaxis should be continued for 3-6 months until immunosuppression is lowered to long-term maintenance level.
For mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are equally effective. For life-threatening CMV disease, intravenous ganciclovir is the first-line treatment, with viral load monitoring to determine treatment duration.
KTR: Epstein Barr Virus (EBV) infection · immunosuppression should be reduced or stopped following the development of post-transplant lymphoproliferative disease (PTLD) · All high-risk (D+/R-) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year · After rejection treatment, EBV viral load should be monitored and immunosuppression reduced.
KTR: Varicella Zoster Virus (VZV) infection
· Primary infection (chickenpox) should be treated with IV aciclovir or oral valaciclovir until the lesions scab over · Uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over · Disseminated (>2 dermatomes), ocular, or invasive shingles should be treated with IV aciclovir until the lesions scab over and immunosuppression should be reduced.
Varicella-susceptible KTRs (VZV IgG negative) with primary VZV exposure should get IVIG, ideally within 96 hours but up to 10 days after exposure. If unavailable or after 10 days, oral aciclovir should be provided for seven days · Patients on the waiting list who are VZV IgG negative should be vaccinated before transplantation, and immunosuppression should be lowered during primary infection.
KTRs with recurrent Herpes Simplex Virus (HSV) infections should consider oral prophylaxis.
KTR: BK virus (BKV) nephropathy · immunosuppression should be reduced to treat confirmed BK (no specific treatment)
KTRs should be tested for BKV virus load using urine microscopy for decoy cells or PCR on urine or serum. Renal biopsy stained for SV40 should confirm suspected BK nephropathy. When serum BKV load surpasses 104 copies/ml, immunosuppression should be lowered. Patients with BK nephropathy from a previous graft can safely undergo re-transplantation.
KTR: Pneumocystis jirovecii infection – treatment and prophylaxis · Co-trimoxazole (15-20mg/kg in three or four separate doses) should be given to all patients for 14–21 days.
Patients with contraindications to co-trimoxazole should get pentamidine (4mg/kg/day intravenously) · Severe disease patients may benefit from adjunctive glucocorticoid therapy Co-trimoxazole 480mg daily for Pneumocystis jirovecii prophylaxis should be given to all renal transplant patients for 3-6 months.
KTR: Hepatitis E virus (HEV)
Hepatitis E Virus (HEV)-screened blood components should be administered to all KTR patients.
Kidney Transplant Recipient:
KTR: Osteoporosis · KTRs with osteoporosis or at high risk should be considered for steroid-avoiding immunosuppression · KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2 · Treatment should follow the Royal College of Physicians (RCP) guidelines for steroid-induced osteoporosis
KTR: Tertiary hyperparathyroidism · Treat severe hyperparathyroidism before transplantation. KTR can be treated with cinacalcet. Treatment should be the same as for other CKD patients.
KTR: Gout · neither allopurinol nor febuxostat should be given with azathioprine · Hyperuricaemia should be treated in KTRs with gout, tophi, or uric acid stones · NSAIDs should be avoided · Oral prednisolone can treat acute gout, while KTR gout can be treated with colchicine.
KTR: Bone pain inhibitor calcineurin
KTRs with intractable bone pain should consider reducing or stopping CNIs and trying dihydropyridine calcium antagonists.
Kidney Transplant Recipient (KTR): Haematological Complications • chronic anaemia should be managed the same way as other patients with CKD · polycythaemia should be treated with ACEIs or ARBs if the haematocrit surpasses 52% in men and 49% in women · refractory instances may be treated with venesection
Kidney Transplant Recipient (KTR): Reproductive Issues · MPA-containing immunosuppressants should be stopped prior to pregnancy and replaced suitably · KTRs should wait one year after transplant and have stable function before trying to conceive. m-TORi should be terminated before conception and replenished as needed. KTRs take 75 mg of aspirin daily from 12 weeks gestation till birth to minimize pre-eclampsia risk. Discuss the risks and benefits of breastfeeding. Contraception recommendations should be like the general population. Male KTRs should be aware that MPA-containing drugs may be teratogenic. KTRs should be informed that m-TORi lower male sperm count and counseled accordingly. Other than m-TORi, male KTRs can utilize all immunosuppressive medications. The danger of putative teratogenicity vs the risk of rejection when switching from MPA to azathioprine should be considered when deciding whether to continue MPA-containing drugs in a male KTR who wants to conceive. Men on m-TORi who want to conceive should quit these agents before conception and replace them as needed. Men who want to retain fertility should avoid m-TORi or bank sperm before taking these medicines. For sexual dysfunction in male KTR without nitrates, Sildenafil is safe and effective.
The BTS guidelines encompasses the duration after transplantation up to the failure of graft.
According to guidelines discussed in detail about clinical infrastructure, drugs level, frequency of visits, patient access to labs, clinic frequency, patient adherence to medication, good diet( after dietician counseling), if any concern psychologist opinion, immunosuppression doses according to trough level, prophylactic drug starting ang stopping according to region of frequency of infections.
If any signs of rejection, failure, opportunistic infection, need of graft biopsy, treatment (ABMR, cellular mediated), and chronic rejection, allograft nephropathy, if any progressive disease treat chronic kidney disease failure consequences accordingly.
Eusha Ansary
2 years ago
Post-Operative Care in the Kidney Transplant Recipient
These guidelines cover the period after renal transplantation, specifically from initial hospital discharge until graft failure or patient death. The management of KTR can be divided into two phases:
a. an early post-operative phase when prevention of acute rejection, optimization of graft function and prevention of opportunistic infection are paramount
b. a later phase when the aims are to preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression – malignancy, infection and premature cardiovascular disease.
1. Kidney Transplant Recipient (KTR):
Organisation of Outpatient Follow-up includes good clinic infrastructure ensuring availability of health care professionals. Clinic frequency suggest that uncomplicated patients may be reviewed progressively in regular interval. All patients should have access to support services and results.
2. Kidney Transplant Recipient: It is important to prevent, detect and take necessary action towards non-adherence in kidney transplant recipients.
3. Kidney Transplant Recipient:
Immunosuppressive treatment
· Induction immunosuppression therapy should take into account the following: Immunosuppressive drugs should be started before or at the time of renal transplantation.
· Induction therapy with biological agents should be administered to all KTRs. In patients at low immunological risk this will generally involve an interleukin-2 receptor antagonist (IL2-RA) and higher immunological risk may be considered for T-cell (lymphocyte) depleting antibodies (TDAs)
· Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance.
· CNI should be started at the time of transplantation and not delayed until the graft is functioning.
· Maintenance immunosuppression should normally consist of a calcineurin inhibitor (CNI) and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs.
· Mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception.
· KTRs who are unable to tolerate tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second line agents such as ciclosporin, sirolimus, everolimus, or belatacept.
· Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients.
4. Kidney Transplant Recipient:
Acute rejection:
Diagnosis of acute rejection: Renal biopsy should be carried out before treating an acute rejection episode unless this will substantially delay treatment or pose a significant risk to the patient. Two cores of renal tissue should be obtained at transplant biopsy since this will increase the sensitivity of the investigation. Routine C4d and SV40 staining should be performed upon transplant biopsies to address other causes of graft dysfunction. Look for human leucocyte antigen (HLA)-specific antibodies in serum at the time of renal biopsy.
Treatment of acute rejection: High dose intravenous corticosteroids should be the first line treatment for acute cellular rejection. Maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection. Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III). Antibody mediated rejection (AMR) should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib. After an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximised (2D)
5. Kidney Transplant Recipient:
Chronic Allograft Injury:
Early identification of graft injury is desirable to maximise the potential for intervention.
Renal function should be monitored at each clinic visit by assessment of serum creatinine and qualitative evaluation of urine protein excretion by dipstick, supplemented by spot protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR)
Renal biopsy is the optimal investigation for parenchymal causes of graft dysfunction where the cause is uncertain
Renal biopsies in patients with chronically deteriorating function should be stained for C4d and SV40
Serum sample should be sent at the time of renal biopsy (for graft dysfunction) to look for HLAspecific antibodies.
Chronic allograft injury should be treated:
-By withdrawal of calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy
-By intensification of immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection)
6. Kidney Transplant Recipient: Cardiovascular Disease and Lifestyle Hypertension
Clinic blood pressure should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
Inhibitors of the renin-angiotensin system may be more effective in the minimisation of proteinuria but should be used with caution in the first 3 months post-transplantResistant hypertension may be due to transplant renal artery stenosis and should be investigated according to local practice Dyslipidaemia
The choice and dose of statin should take into account concurrent immunosuppression. High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/calcium channel antagonists Diabetes mellitus
The diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting
or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing
A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression Ischaemic heart disease
We suggest that KTRs receive standard treatment for ischaemic heart disease, including thrombolysis, revascularisation, and secondary prevention Smoking cessation
Smoking should be strongly discouraged in transplant recipient Lifestyle measures
Maintenance of a healthy diet should be encouraged
An ideal weight should be targeted (body mass index (BMI) ≤25 kg/m2)
Weight management services should be available
Screening of cancer, Vaccination and treatment of infection.
Level of evidence 5
Huda Al-Taee
2 years ago
Clinic infrastructure:
A consultant-level healthcare professional should be available for every transplant clinic.
KTRs should be reviewed in a dedicated outpatient area.
The results of blood tests (including drug levels, if possible) should be available within 24 hours.
A formal mechanism should exist for results review by healthcare professionals within 24 hours of a clinic appointment.
There should be access to a multidisciplinary renal team, including a pharmacist, dietician, social worker and psychologist.
Patient care should be planned along principles set out in the National Service Framework and “Kidney Health Delivering Excellence”.
Clinic frequency
2-3 times weekly for the first month after transplantation.
1-2 times weekly for months 2-3.
Every 2-4 weeks for months 4-6.
Every 4-6 weeks for months 6-12.
3-6 monthly thereafter.
Patient Access
All patients should have the option of online access to their results via the “Patient View” service.
All patients should have open access to the renal transplant outpatient service and have an established point of contact for enquiries.
Patient information should be available in both written and electronic formats.
Chronic transplant care review
A process should exist for patient review on an annual basis in a different format of a clinic according to the “Care plan model”.
This should be a patient-centred clinic, facilitated by a healthcare professional.
It should address concerns in medical, social, psychological and sexual domains.
Access to a renal dietician, social worker, specialist renal pharmacist and/or psychologist should be readily available from this clinic.
This process should proceed in parallel with a formal medical review
Recognising non-adherence
Factors associated with non-adherence should be identified.
An established interventional pathway should be in place for those at high risk of or with proven nonadherence.
Pathways should be in place for paediatric KTRs in transition and for adolescent KTRs.
Immunosuppression regimen
patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression.
Induction immunosuppression
Immunosuppressive drugs should be started before or at the time of renal transplantation.
Induction therapy with biological agents should be administered to all KTRs. In patients at low immunological risk, this will generally involve an interleukin-2 receptor antagonist (IL2-RA). Recipients at higher immunological risk may be considered for T-cell-depleting antibodies.
Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance.
CNI should be started at the time of transplantation and not delayed until the graft is functioning.
KTR: Maintenance immunosuppression
maintenance immunosuppression should normally consist of a calcineurin inhibitor and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs.
low-medium dose tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice in patients also taking steroids who are low and medium immunological risk and are not at high risk of developing post transplant diabetes mellitus.
mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception.
slow release tacrolimus may be used as an option as second line agents for patients who suffer intolerable side effects related to peak dose toxicity.
KTRs who are unable to tolerate tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second-line agents such as ciclosporin, sirolimus, everolimus, or belatacept.
MPA-based drugs should be the first-line antiproliferative agent, in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception.
mycophenolate mofetil and enteric-coated mycophenolate sodium provide equivalent maintenance immunosuppression.
steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients.
aiming for minimum target levels for CNIs in uncomplicated renal transplantation after 3 months.
CNIs should not be withdrawn.
t if steroids are not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less).
long-term monitoring of immunosuppression levels is required as follows:
Tacrolimus and ciclosporin levels should be monitored. The initial frequency should be three times a week. Levels should also be checked when any medication with possible interactions is prescribed, the dosage is changed, the formulation is changed, or when there is unexplained graft dysfunction.
Tacrolimus should be monitored by the trough (C0) level, while ciclosporin can be monitored by either C0 or 2- hour post dose (C2).
Tacrolimus and ciclosporin levels should be available within 24 hours of taking blood samples in the first three months after transplantation.
The utility of monitoring mycophenolic acid (MPA) C0 levels is uncertain.
Sirolimus should be monitored by the C0 trough level.
Prescribing and the use of generic agents
generic immunosuppression compounds should not be used unless they have been shown to be bioequivalent and approved by the European Agency for the Evaluation of Medicinal Products.
KTRs should be made aware of the existence of generics and the importance of not switching between preparations without appropriate supervision.
drugs should be prescribed by brand name.
KTRs should be closely monitored after switching between generic preparations until a new steady state is established.
Diagnosis of acute rejection
a transplant renal biopsy should be carried out before treating an acute rejection episode unless this will substantially delay treatment or pose a significant risk to the patient.
two cores of renal tissue should be obtained at transplant biopsy since this will increase the sensitivity of the investigation.
a 16 gauge automated core biopsy needle is used where possible to provide the best compromise between diagnostic usefulness and patient tolerance of the procedure.
a protocol transplant renal biopsy, defined as a biopsy performed in a stable graft without clinical evidence of acute rejection, be considered in the setting of persisting delayed graft function.
routine C4d and SV40 staining should be performed upon transplant biopsies to address other causes of graft dysfunction.
a serum sample be sent at the time of renal biopsy (for graft dysfunction) to look for HLA-specific antibodies.
Treatment of acute rejection
borderline acute cellular rejection should be treated in the context of acute graft dysfunction.
high dose intravenous corticosteroids should be the first line treatment for acute cellular rejection.
maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type.
lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III).
antibody mediated rejection should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib.
BTS guidelines on antibody incompatible transplantation for management of rejection in the context of antibody incompatible transplantation.
after an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximised.
Diagnosis of Chronic Allograft Injury
early identification of graft injury is desirable to maximise the potential for intervention. A proactive and systematic approach should employed to manage graft dysfunction.
Detection of Chronic Allograft Injury
renal function should be monitored at each clinic visit by assessment of serum creatinine and qualitative evaluation of urine protein excretion by dipstick, supplemented by spot protein:creatinine ratio or albumin:creatinine ratio if positive.
Diagnosis of Chronic Allograft Injury
renal biopsy is the optimal investigation for parenchymal causes of graft dysfunction where the cause is uncertain.
renal biopsies in patients with chronically deteriorating function should be stained for C4d and SV40.
a serum sample should be sent at the time of renal biopsy (for graft dysfunction) to look for HLA-specific antibodies.
Treatment of chronic allograft injury
By withdrawal of calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy.
By intensification of immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection).
In a similar fashion to other patients with chronic kidney disease (CKD), following similar preventative strategies and with timely referral to low clearance services.
Renal biopsy in chronic allograft injury
If there is a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy-proven acute rejection.
Every 7-10 days during delayed graft function.
If expected renal function is not achieved within 4-8 weeks.
If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol).
Hypertension
Blood pressure should be recorded at each clinic visit.
Clinic blood pressure should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35).
Home blood pressure recordings and 24-hour ambulatory recordings may be helpful in some instances but lower BP targets should then be set (home and or ambulatory daytime measures <135/80mmHg).
There is no evidence that any antihypertensive agent is better than any other and effort should be focused on achieving absolute blood pressure control rather than the use of individual agents.
Inhibitors of the renin-angiotensin system may be more effective in the minimisation of proteinuria but should be used with caution in the first 3 months post-transplant.
Resistant hypertension may be due to transplant renal artery stenosis and should be investigated according to local practice.
Dyslipidemia
Fasting lipid levels should be measured on an annual basis in renal transplant recipients.
Treatment targets should be the same as in the general population.
KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease.
The choice and dose of statin should take into account concurrent immunosuppression. High-dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/or calcium channel antagonists.
Diabetes mellitus
Screening for the development of post-transplant diabetes mellitus (PTDM) by dipstick urinalysis and measurement of blood sugar level at each clinic visit.
Post-transplant immunosuppression should take into account risk factors for the development of diabetes.
The diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing.
A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression.
Post-transplant diabetes should be managed in collaboration with specialists in diabetic medicine.
All units should have a protocol for the management of post-transplant diabetes.
KTR with diabetes (either prior to transplantation or PTDM) should undergo screening for diabetic complications (retinal screening, foot care, neuropathy) in line with guidelines for non-KTR patients with diabetes.
Ischaemic heart disease
KTRs receive standard treatment for ischaemic heart disease, including thrombolysis, revascularisation, and secondary prevention.
Smoking cessation
smoking should be strongly discouraged in transplant recipients.
Lifestyle measures
Maintenance of a healthy diet should be encouraged.
An ideal weight should be targeted (body mass index (BMI) ≤25 kg/m2 ).
Weight management services should be available.
We suggest that KTRs participate in physical activity at a level similar to that recommended to age and comorbidity-matched counterparts from the general population.
Alcohol consumption should be within national guidelines.
Recreational drug use should be avoided.
The use of over-the-counter medications (without discussion with clinical staff) and non-proprietary medications (e.g. herbal medicines) should be discouraged.
Screening for cancer
Screening should be similar to the general population for cervical, breast, colon and prostate cancer.
Screening is not recommended for renal cell carcinoma.
Patient education pre and post-transplantation.
Patients should be aware of malignancy risk and encouraged to report symptoms which may represent de novo malignancy (e.g. breast or testicular lumps).
Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant.
Patients with cirrhosis should undergo an annual hepatic ultrasound and determination of serum alpha-fetoprotein.
Non-melanoma skin cancer
KTRs should be educated about the adverse effects of sun exposure.
an individualised assessment of hazards should be made according to risk factors.
patients should be encouraged to cover their skin in direct sunlight and to use total sunblock (Sun Protection Factor ≥50).
self-examination should be encouraged with guidance provided. This should be supplemented by at least a biannual review by a trained healthcare professional up to 5 years post-transplant and an annual review from 5 years.
the prescription of acitretin as chemoprophylaxis be considered in those with ≥2 previous NMSC if there are no contraindications.
Immunosuppression in cancers
immunosuppression should be reduced if neoplasia develops.
mammalian target of rapamycin inhibitors (m-TORi) are considered as alternative immunosuppressive agents in KTRs who develop de novo malignancy.
Vaccination
Should be vaccinated with inactivated viruses as per the normal population.
Should receive annual influenza vaccination unless contraindicated.
Should have hepatitis B surface antibody (HBsAb) levels rechecked annually and be revaccinated if antibody titres fall below 10 mIU/mL.
Should not receive live attenuated vaccines.
Should receive the pneumococcal vaccine and a booster every five years.
Prophylaxis and treatment of CMV disease
Prophylaxis should be continued for 3-6 months, until immunosuppression has been reduced to long-term maintenance level.
Treatment should be administered for 6 weeks after treatment with a TDA.
All transplant units should be able to measure CMV serological status and quantify viral load.
Donor and recipient CMV status should be recorded at the time of transplantation.
Each unit should have a written protocolised CMV strategy based on prophylaxis or pre-emptive therapy.
For the treatment of mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are of equivalent efficacy.
The first line treatment of for life-threatening CMV disease is intravenous ganciclovir.
Treatment duration should be determined by monitoring viral load.
EBV infection
immunosuppression should be reduced or stopped following the development of post-transplant lymphoproliferative disease.
Both donor and recipient should have their EBV serology recorded at the time of transplantation.
All high-risk (D+ /R- ) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year.
EBV viral load should be monitored after the treatment of rejection.
Total immunosuppression should be reduced when EBV titres rise significantly.
VZV infection
Primary infection (chickenpox) should be treated with intravenous acyclovir or oral valacyclovir until the lesions scab over.
Uncomplicated shingles should be treated with oral acyclovir or valacyclovir until the lesions scab over.
Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with intravenous acyclovir until the lesions scab over, together with a reduction in immunosuppression.
Varicella-susceptible KTRs (i.e. VZV IgG negative) with primary exposure to VZV should receive intravenous immunoglobulin, ideally within 96 hours, but up to a maximum of 10 days following exposure. If unavailable or after 10 days, oral acyclovir should be prescribed for seven days.
Patients on the waiting list who are VZV IgG negative should be vaccinated prior to transplantation.
Immunosuppression should be reduced during primary infection.
HSV infection
Superficial HSV infection should be treated with appropriate oral agents until the lesions have resolved.
Systemic HSV infections should be treated with intravenous acyclovir and a reduction in immunosuppression until a response occurs, and oral medication should be continued for at least 14 days.
KTRs suffering frequent recurrent HSV infections should consider oral prophylaxis.
BK nephropathy
confirmed BK nephropathy should be treated by reduction in immunosuppression.
Screening should also be carried out when renal function deteriorates in an unexplained fashion.
KTRs should be screened for BKV viral load by performing urine microscopy for decoy cells or by polymerase chain reaction (PCR) on urine or serum.
Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40. Two cores containing medullary tissue should ideally be examined.
Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml.
There is no established specific treatment for BK nephropathy.
Re-transplantation can safely be considered in patients who have BK nephropathy diagnosed in an earlier graft.
Pneumocystis jirovecii infection – treatment and prophylaxis
All patients with confirmation (microscopy or PCR) of Pneumocystis jirovecii in respiratory secretions should be treated for 14 to 21 days with co-trimoxazole orally or intravenously (15-20mg/kg in three or four divided doses).
Patients with contraindications to treatment with co-trimoxazole should receive pentamidine (4mg/kg/day intravenously).
Adjunctive glucocorticoid therapy may be considered in patients with severe disease.
All patients should receive 3-6 months of treatment with co-trimoxazole 480mg daily for Pneumocystis jirovecii prophylaxis following renal transplantation.
Post-transplant infection prophylaxis
All patients should receive 3-6 months of treatment with co-trimoxazole 480 mg daily.
Oral antifungal prophylaxis should be administered for one week after transplantation.
In selected patients, prophylaxis against mycobacterium tuberculosis with daily isoniazid (supplemented with pyridoxine) should be instituted for six months after transplantation.
Hepatitis E Virus
Hepatitis E Virus (HEV)-screened blood components should be given to all KTR.
Osteoporosis
KTRs suffering from osteoporosis or at high potential risk should be considered for steroid-avoiding immunosuppression.
KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2.
Treatment should be according to the Royal College of Physicians (RCP) guidelines for steroid-induced osteoporosis.
Tertiary hyperparathyroidism
Severe hyperparathyroidism should be treated prior to transplantation.
Cinacalcet can be used in KTR.
Treatment should be the same as for other patients with CKD.
Treatment of gout
neither allopurinol nor febuxostat should be administered with azathioprine.
Hyperuricemia should be treated when associated with gout, tophi or uric acid stones.
Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided in KTRs.
Acute gout may be treated with brief a course of oral prednisolone.
Colchicine is an effective treatment for gout in KTR.
Calcineurin inhibitor bone pain
Reduction or withdrawal of CNIs should be considered in KTRs with intractable bone pain.
Dihydropyridine calcium antagonists also may be beneficial.
Anaemia
chronic anaemia should be managed in the same way as other patients with CKD.
Polycythaemia
initial treatment should be with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
Haemoglobin levels should be monitored at every clinic visit.
Treatment should be initiated if the haematocrit or packed cell volume exceeds 52% in men and 49% in women.
Venesection may be used in refractory cases.
Conception and contraception
MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately.
KTRs should wait for one year after transplant and have stable function before attempting conception.
Counselling regarding fertility and reproduction should be offered to female KTRs and their partners either prior to transplantation or soon afterwards.
m-TORi should be stopped prior to conception and replaced as appropriate.
Pregnancy should be jointly managed with an Obstetrics department with experience of care of KTR.
KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth of the baby unless there are contraindications.
The risks and benefits of breastfeeding should be discussed.
Contraception advice should be similar to the general population.
Conception and contraception (male)
Male KTRs are advised that MPA containing have theoretical teratogenic potential in men taking these agents.
KTRs should be advised that m-TORi reduce the male sperm count and counselled accordingly.
All immunosuppressive drugs other than m-TORi can be used in male KTRs.
The decision to continue MPA containing compounds in a male KTR wishing to conceive should balance the risk of theoretical teratogenicity against the risk of rejection on changing from MPA to azathioprine.
Men on m-TORi who wish to conceive should discontinue these agents prior to conception and replace them as appropriate.
Men who wish to maintain fertility should avoid m-TORi or bank sperm prior to starting these drugs.
Sexual dysfunction
Specific enquiries should be made regarding sexual dysfunction, preferably at an annual review clinic.
Care pathways for dealing with sexual dysfunction should be established.
Close liaison with local andrology service is recommended.
Sildenafil is safe and effective in male KTR not taking nitrates.
Level of Evidence:
Level 1 (clinical practice guidelines).
Zahid Nabi
2 years ago
These guidelines are an umbrella document for management of kidney transplant patients starting from developing an infrastructure till close monitoring of these patients covering both clinical and non clinical aspects of management.These guidelines are developed for Non experts but found them useful for any transplant program which wants to provide a standard of care to these patients.
The guidelines cover the areas like
Transplant clinic Logestics
Follow up visits schedule like frequently intially
Immunosupression protocols and how to follow them and intervention when needed
Check of adherence
Post transplant immunization and screening
life style modification and management of HTN , DM and dyslipidemia and ischemic heart disease
Post transplant prophylaxis like CMV , PCP and diagnosing BKVAN early and intervening accordingly
Reproductive issues after transplant
It’s basically a complete document and all transplant programs should follow this in true letter and spirit to provide best possible care to their patients
Hussam Juda
2 years ago
Post-Operative Care in the Kidney Transplant Recipient Introduction
· This document is for nonexpert workers in the care of kidney transplant recipients
· The following guidelines meant with healthcare professionals, medical and surgical trainees, general practitioners, nurse specialists, all who deal with kidney transplant patients
· The management of KTR can be divided into two phases:
a. an early post-operative phase when prevention of acute rejection, optimization of graft function and prevention of opportunistic infection are paramount
b. a later phase when the aims are to preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression – malignancy, infection and premature cardiovascular disease.
Summary of Clinical Practice Guidelines for the Post-Operative Care of the Kidney Transplant Recipient
1.Kidney Transplant Recipient (KTR): Organisation of Outpatient Follow-up KTR: Clinic infrastructure
· Every transplant clinic should be covered by consultant
· KTRs should be reviewed in a dedicated outpatient area
· The results of blood tests should be available within 24 hours
· There should be access to a multidisciplinary renal team including pharmacist, dietician, social worker and psychologist KTR: Clinic frequency
uncomplicated patients may be reviewed progressively less frequently (2C)
· 2-3 times weekly for the first month after transplantation
· 1-2 times weekly for months 2-3
· Every 2-4 weeks for months 4-6
· Every 4-6 weeks for months 6-12
· 3-6 monthly thereafter KTR: Patient access
all patients should have access to support services and results. (2C) KTR: Chronic transplant care review
a detailed review should be performed annually post-operatively (2C)
2. Kidney Transplant Recipient: Non-adherence KTR: Recognising non-adherence
it is important to prevent and detect non-adherence in kidney transplant recipients. (2C) 3. Kidney Transplant Recipient: Immunosuppressive treatment
the patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression (1D) KTR: Induction immunosuppression
· Immunosuppressive drugs should be started before or at the time of renal transplantation (1B)
· Induction therapy with biological agents should be administered to all KTRs.
1)an interleukin-2 receptor antagonist (IL2-RA) for patients with low immunological risk .
2) T-cell (lymphocyte) depleting antibodies (TDAs) for higher immunological risk
· Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance (1C) KTR: Induction immunosuppression
· a CNI should be started at the time of transplantation and not delayed until the graft is functioning (2C)
KTR: Maintenance immunosuppression
· should normally consist of a CNI and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs (1B)
· tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice in patients also taking steroids who are low and medium immunological risk and are not at high risk of developing post transplant diabetes mellitus (PTDM) (2C)
· mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B
· slow release tacrolimus may be used as an option as second line agents for patients who suffer intolerable side effects related to peak dose toxicity (2C)
· the use of second line agents such as ciclosporin, sirolimus, everolimus, or belatacept, if tacrolimus was not tolerated
· MPA-based drugs should be the first-line antiproliferative agent, in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B)
· MMF and enteric-coated mycophenolate sodium provide equivalent maintenance immunosuppression (2B)
· steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients (2B)
· minimum target levels for CNIs in uncomplicated renal transplantation after 3 months
· CNIs should not be withdrawn (2B)
· t if steroids are not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less) (2C) KTR: Monitoring of immunosuppression
· Tacrolimus and ciclosporin levels should be monitored three times a week initially
· Levels should also be checked if: 1) new drug given 2) the dosage or formulation is changed
3) unexplained graft dysfunction
· Tacrolimus and ciclosporin levels should be available within 24 hours of taking blood samples in the first three months after transplantation
· Sirolimus should be monitored by the C0 trough level 4. Kidney Transplant Recipient: Acute rejection KTR: Diagnosis of acute rejection
· a transplant renal biopsy should be done before treating an acute rejection episode unless this will delay treatment or pose a significant risk to the patient
· two cores of renal tissue should be obtained at transplant biopsy
· a 16-gauge automated core biopsy needle is suggested to be used
· a protocol transplant renal biopsy is recommended for persisting delayed graft function
· routine C4d and SV40 staining should be performed upon transplant biopsies to address other causes of graft dysfunction
· a serum sample to be sent at the time of renal biopsy (for graft dysfunction) to look for HLA-specific antibodies
KTR: Treatment of acute rejection
· high dose intravenous corticosteroids should be the first line treatment for acute cellular rejection
· maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type
· Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e., Banff category 4 Type II and III)
· AMR should be treated with one or more of the following modalities: steroids; plasma exchange; IVIG; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib
· after an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximized
5. Kidney Transplant Recipient: Chronic Allograft Injury
· renal biopsies in patients with chronically deteriorating function should be stained for C4d and SV40
KTR: Treatment of chronic allograft injury
· By withdrawal of calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy
· By intensification of immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection)
· In a similar fashion to other patients with chronic kidney disease (CKD), following similar preventative strategies and with timely referral to low clearance services
KTR: Renal biopsy in chronic allograft injury. Indicated if:
· a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection
· Every 7-10 days during delayed graft function (DGF)
· If expected renal function is not achieved within 4-8 weeks
· If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol)
6. Kidney Transplant Recipient: Cardiovascular Disease and Lifestyle KTR: Hypertension
· Blood pressure should be recorded at each clinic visit and should be <140/90 mmHg in clinic
· There is no evidence that any antihypertensive agent is better than any other
· RAS Inhibitors may be more effective in treatment of proteinuria
· Resistant hypertension may be due to transplant renal artery stenosis and should be investigated
KTR: Dyslipidaemia
· Fasting lipid levels should be measured on an annual basis and treat as in the general population
· KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease
· High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/calcium channel antagonists
KTR: Diabetes mellitus
· Screening for post-transplant DM (PTDM) by dipstick urinalysis and measurement of blood sugar level at each clinic visit
· Consider WHO criteria for the diagnosis of DM based on fasting or random blood, serum HBA1c or OGTT
· A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression and should be managed in collaboration with Diabetologist.
· KTR with diabetes should undergo screening for diabetic complications
KTR: Ischaemic heart disease
· KTRs can receive standard treatment for ischaemic heart disease, including thrombolysis, revascularisation, and secondary prevention
· smoking should be strongly discouraged in transplant recipients
KTR: Lifestyle measures
· a healthy diet and body mass index (BMI) ≤25 kg/m2
· Limited alcohol consumption and avoidance recreational drug use
· Discourage the use of over-the-counter medications and herbal medicines.
7. Kidney Transplant Recipient: Neoplasia
· Screening should be similar to the general population for cervical, breast, colon and prostate cancer and not recommended for renal cell carcinoma
· Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant
· Patients with cirrhosis should undergo an annual hepatic ultrasound and determination of serum alpha fetoprotein
· KTRs should be educated about the adverse effects of sun exposure and to cover their skin in direct sunlight and to use total sunbloc
· self-examination should be encouraged with guidance provided, at least biannual review by a up to 5 years post-transplant and annual review from 5 years
· Consider acitretin as chemoprophylaxis for those with ≥2 previous Non-melanoma skin cancer if there are no contraindications
· immunosuppression should be reduced if neoplasia develops and consider m-TORi as alternative immunosuppressive agent
· m-TORs have specific anti-tumor effects in Kaposi sarcoma
Kidney Transplant Recipient: Infection Complications KTR: Vaccination
· KTRs Should be vaccinated with inactivated viruses as per the normal population and receive annual influenza vaccination unless contraindicated
· KTRs Should have HBsAb levels rechecked annually and be revaccinated if antibody titres fall below 10 mIU/mL
· KTRs Should not receive live attenuated vaccines
· KTRs Should receive pneumococcal vaccine and a booster every five years KTR: Cytomegalovirus (CMV) disease
· Prophylaxis should be continued for 3-6 months, until immunosuppression has been reduced to long-term maintenance level
· Treatment should be administered for 6 weeks after treatment with a TDA
· For the treatment of mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are of equivalent efficacy
· The first line treatment of life-threatening CMV disease is intravenous ganciclovir with monitoring viral load to assess duration of treatment
KTR: Epstein Barr Virus (EBV) infection
· immunosuppression should be reduced or stopped following the development of post- transplant lymphoproliferative disease (PTLD)
· All high risk (D+ /R-) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year
· EBV viral load should be monitored after the treatment of rejection, with reduction of immunosuppression when EBV titres rise significantly
KTR: Varicella Zoster Virus (VZV) infection
· Primary infection (chickenpox) should be treated with IV aciclovir or oral valaciclovir until the lesions scab over
· Uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over
· Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with IV aciclovir until the lesions scab over, together with a reduction in immunosuppression
· Varicella-susceptible KTRs (i.e. VZV IgG negative) with primary exposure to VZV should receive IVIG, ideally within 96 hours, but up to a maximum of 10 days following exposure. If unavailable or after 10 days, oral aciclovir should be prescribed for seven days
· Patients on the waiting list who are VZV IgG negative should be vaccinated prior to transplantation, and Immunosuppression should be reduced during primary infection
KTR: Herpes Simplex Virus (HSV) infection
· KTRs suffering frequent recurrent HSV infection should consider oral prophylaxis KTR: BK virus (BKV) nephropathy
· confirmed BK nephropathy should be treated by reduction in immunosuppression (no specific treatment)
· KTRs should be screened for BKV viral load or by performing urine microscopy for decoy cells or by PCR on urine or serum
· Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40
· Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml
· Re-transplantation can safely be considered in patients who have BK nephropathy diagnosed in an earlier graft
KTR: Pneumocystis jirovecii infection – treatment and prophylaxis
· All patients with Pneumocystis jirovecii should be treated for 14 to 21 days with co-trimoxazole orally or intravenously (15-20mg/kg in three or four divided doses)
· Patients with contraindications to treatment with co-trimoxazole should receive pentamidine (4mg/kg/day intravenously)
· Adjunctive glucocorticoid therapy may be considered in patients with severe disease
· All patients should receive 3-6 months of treatment with co-trimoxazole 480mg daily for Pneumocystis jirovecii prophylaxis following renal transplantation KTR: Hepatitis E Virus (HEV)
Hepatitis E Virus (HEV)-screened blood components should be given to all KTR
Kidney Transplant Recipient: Bone and Joint Disease KTR: Osteoporosis
· KTRs suffering from osteoporosis or at high potential risk should be considered for steroid-avoiding immunosuppression
· KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2
· Treatment should be according to the Royal College of Physicians (RCP) guidelines for steroid-induced osteoporosis
KTR: Tertiary hyperparathyroidism
· Severe hyperparathyroidism should be treated prior to transplantation
· Cinacalcet can be used in KTR
· Treatment should be the same as for other patients with CKD
KTR: Gout
· neither allopurinol nor febuxostat should be administered with azathioprine
· Hyperuricaemia should be treated when associated with gout, tophi or uric acid stones
· NSAIDs should be avoided in KTRs
· Acute gout may be treated with brief a course of oral prednisolone, and Colchicine is an effective treatment for gout in KTR KTR: Calcineurin inhibitor bone pain
· Reduction or withdrawal of CNIs should be considered in KTRs with intractable bone pain
· Dihydropyridine calcium antagonists also may be beneficial
Kidney Transplant Recipient (KTR): Haematological Complications
· chronic anaemia should be managed in the same way as other patients with CKD
· Polycythaemia initial treatment should be with ACEIs or ARBs, if the haematocrit or exceeds 52% in men and 49% in women
· Venesection may be used in refractory Polycythaemia cases
Kidney Transplant Recipient (KTR): Reproductive Issues
· MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately
· KTRs should wait for one year after transplant and have stable function before attempting conception
· m-TORi should be stopped prior to conception and replaced as appropriate
· KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth of the baby unless there are contraindications
· The risks and benefits of breastfeeding should be discussed
· Contraception advice should be similar to the general population
· Male KTRs are advised that MPA containing compounds have theoretical teratogenic potential in men taking these agents
· KTRs should be advised that m-TORi reduce the male sperm count and counselled accordingly
· All immunosuppressive drugs other than m-TORi can be used in male KTRs
· The decision to continue MPA containing compounds in a male KTR wishing to conceive should balance the risk of theoretical teratogenicity against the risk of rejection on changing from MPA to azathioprine
· Men on m-TORi who wish to conceive should discontinue these agents prior to conception and replace them as appropriate
· Men who wish to maintain fertility should avoid m-TORi or bank sperm prior to starting these drugs
· For sexual dysfunction Sildenafil is safe and effective in male KTR not taking nitrates
This is Editorials evidence 5
Assafi Mohammed
2 years ago
Summary of the article “Post-Operative Care in the Kidney Transplant Recipient (BTS GUIDELINES- 2017)” KTR: Clinic frequency
We suggest that uncomplicated patients may be reviewed progressively less frequently (2C)
· 2-3 times weekly for the first month after transplantation
· 1-2 times weekly for months 2-3
· Every 2-4 weeks for months 4-6
· Every 4-6 weeks for months 6-12
· 3-6 monthly thereafter KTR: immunosuppression regimen
We recommend that the patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression (1D) KTR: Induction immunosuppression
We recommend induction therapy should take into account the following: · Immunosuppressive drugs should be started before or at the time of renal transplantation (1B) · Induction therapy with biological agents should be administered to all KTRs. In patients at low immunological risk this will generally involve an interleukin-2 receptor antagonist (IL2-RA). Recipients at higher immunological risk may be considered for T-cell (lymphocyte) depleting antibodies (TDAs)(1B) · Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance (1C) KTR: Induction immunosuppression · We suggest that a CNI should be started at the time of transplantation and not delayed until the graft is functioning (2C) . KTR: Maintenance immunosuppression · We recommend that maintenance immunosuppression should normally consist of a calcineurin inhibitor (CNI) and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs (1B). · We suggest that low-medium dose tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice in patients also taking steroids who are low and medium immunological risk and are not at high risk of developing post transplant diabetes mellitus (PTDM) (2C). · We suggest that mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B). · We suggest that slow release tacrolimus may be used as an option as second line agents for patients who suffer intolerable side effects related to peak dose toxicity (2C). · We suggest that KTRs who are unable to tolerate tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second line agents such as ciclosporin, sirolimus, everolimus, or belatacept (1B) · We suggest that MPA-based drugs should be the first-line antiproliferative agent, in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B). · We suggest that mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (Myfortic®) provide equivalent maintenance immunosuppression (2B) · We suggest that steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients (2B) · We suggest aiming for minimum target levels for CNIs in uncomplicated renal transplantation after 3 months (2C) · We suggest that CNIs should not be withdrawn (2B) · We suggest that if steroids are not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less) (2C) KTR: Monitoring of immunosuppression
We suggest that long-term monitoring of immunosuppression levels is required as follows: · Tacrolimus and ciclosporin levels should be monitored. The initial frequency should be three times a week. Levels should also be checked when any medication with possible interactions is prescribed, the dosage is changed, the formulation is changed, or when there is unexplained graft dysfunction (2C) · Tacrolimus should be monitored by the trough (C0) level, while ciclosporin can be monitored by either C0 or 2- hour post dose (C2) level (2C) · Tacrolimus and ciclosporin levels should be available within 24 hours of taking blood samples in the first three months after transplantation (2D) · The utility of monitoring mycophenolic acid (MPA) C0 levels is uncertain (2D) · Sirolimus should be monitored by the C0 trough level (2C)
KTR: Prescribing and the use of generic agents · We suggest that generic immunosuppression compounds should not be used unless they have been shown to be bioequivalent and approved by the European Agency for the Evaluation of Medicinal Products (2D). · We suggest that KTRs should be made aware of the existence of generics and the importance of not switching between preparations without appropriate supervision (2D) · We suggest that drugs should be prescribed by brand name (whether branded or generic drugs are prescribed) (2D) · We suggest that KTRs should be closely monitored after switching between generic preparations until a new steady state is established (2D)
KTR:Acute rejection a) Diagnosis of acute rejection · We recommend that a transplant renal biopsy should be carried out before treating an acute rejection episode unless this will substantially delay treatment or pose a significant risk to the patient (1C) · We recommend that a transplant renal biopsy should be carried out before treating an acute rejection episode unless this will substantially delay treatment or pose a significant risk to the patient (1C) · We suggest that two cores of renal tissue should be obtained at transplant biopsy since this will increase the sensitivity of the investigation (2C) · We suggest that a 16 gauge automated core biopsy needle is used where possible to provide the best compromise between diagnostic usefulness and patient tolerance of the procedure (1C) · We recommend that a protocol transplant renal biopsy, defined as a biopsy performed in a stable graft without clinical evidence of acute rejection, be considered in the setting of persisting delayed graft function (1C) · We recommend that routine C4d and SV40 staining should be performed upon transplant biopsies to address other causes of graft dysfunction (2C) · We suggest that a serum sample be sent at the time of renal biopsy (for graft dysfunction) to look for human leucocyte antigen (HLA)-specific antibodies (2C) b) KTR: Treatment of acute rejection · We suggest that borderline acute cellular rejection should be treated in the context of acute graft dysfunction (2D) · We recommend that high dose intravenous corticosteroids should be the first line treatment for acute cellular rejection (1D) · We suggest that maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type (2D) · We suggest that lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III) (2C) · We suggest that antibody mediated rejection (AMR) should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib (2C) · We recommend that the British Transplant Society (BTS) guidelines on antibody incompatible transplantation for management of rejection in the context of antibody incompatible transplantation (1A-D) · We suggest that – after an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximised (2D) KTR: Chronic Allograft Injury a) KTR:Diagnosis of Chronic Allograft Injury · We recommend that early identification of graft injury is desirable to maximise the potential for intervention. A proactive and systematic approach should employed to manage graft dysfunction (1C) · We suggest that renal function should be monitored at each clinic visit by assessment of serum creatinine and qualitative evaluation of urine protein excretion by dipstick, supplemented by spot protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR) if positive (2C) · We suggest that renal biopsy is the optimal investigation for parenchymal causes of graft dysfunction where the cause is uncertain (2C) · We suggest that renal biopsies in patients with chronically deteriorating function should be stained for C4d and SV40 (2C) · We suggest that a serum sample should be sent at the time of renal biopsy (for graft dysfunction) to look for HLA- specific antibodies (2C) b) KTR: Treatment of chronic allograft injury
We suggest that chronic allograft injury should be treated: · By withdrawal of calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy (2C) · By intensification of immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection) (2C) · In a similar fashion to other patients with chronic kidney disease (CKD), following similar preventative strategies and with timely referral to low clearance services (2D) c) KTR: Renal biopsy in chronic allograft injury
We suggest that a renal transplant biopsy is indicated: · If there is a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection (BPAR) (1C) · Every 7-10 days during delayed graft function (DGF) (2C) · If expected renal function is not achieved within 4-8 weeks (2D) · If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol) (2C)
KTR:Cardiovascular Disease and Life style a) KTR: Hypertension We suggest that the management of hypertension take into account that: · Blood pressure should be recorded at each clinic visit (1C) · Clinic blood pressure should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35) (2C) · Home blood pressure recordings and 24-hour ambulatory recordings may be helpful in some instances but lower BP targets should then be set (home and or ambulatory daytime measures <135/80mmHg) (2D) · There is no evidence that any antihypertensive agent is better than any other and effort should be focused on achieving absolute blood pressure control rather than the use of individual agents (2D) · Inhibitors of the renin-angiotensin system may be more effective in the minimisation of proteinuria but should be used with caution in the first 3 months post-transplant.(2C) · Resistant hypertension may be due to transplant renal artery stenosis and should be investigated according to local practice (2D) b) KTR: Dyslipidaemia
We suggest that the management of dyslipidaemia take into account that: · Fasting lipid levels should be measured on an annual basis in renal transplant recipients (2C) · Treatment targets should be the same as in the general population (2C) · KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease (2C) · The choice and dose of statin should take into account concurrent immunosuppression. High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/calcium channel antagonists (2D) c) KTR: Diabetes mellitus
We suggest that the detection and treatment of diabetes should consider: · Screening for the development of post-transplant diabetes mellitus (PTDM) by dipstick urinalysis and measurement of blood sugar level at each clinic visit (2C) · Post-transplant immunosuppression should take into account risk factors for the development of diabetes (2C) · The diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing (1C) · A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression (2D) · Post-transplant diabetes should be managed in collaboration with specialists in diabetic medicine (2D) · All units should have a protocol for the management of post-transplant diabetes (2C) · KTR with diabetes (either prior to transplantation or PTDM) should undergo screening for diabetic complications (retinal screening, foot care, neuropathy) in line with guidelines for non KTR patients with diabetes (2D) d) KTR: Ischaemic heart disease · We suggest that KTRs receive standard treatment for ischaemic heart disease, including thrombolysis, revascularisation, and secondary prevention (2C)
e) KTR: Smoking cessation · We recommend that smoking should be strongly discouraged in transplant recipients (see guideline 6.4) (1A) f) KTR: Lifestyle measures
We suggest that advice on healthy lifestyle forms a routine part of post-transplant care: · Maintenance of a healthy diet should be encouraged (2C) · An ideal weight should be targeted (body mass index (BMI) ≤25 kg/m2) (2C) · Weight management services should be available (2C) · We suggest that KTRs participate in physical activity at a level similar to that recommended to age and comorbidity matched counterparts from the general population (2D) · Alcohol consumption should be within national guidelines (2D) · Recreational drug use should be avoided (2D) · The use of over-the-counter medications (without discussion with clinical staff) and non-proprietary medications (e.g. herbal medicines) should be discouraged (2D)
KTR:Neoplasia a) KTR: Screening for cancer
We suggest that the organisation of screening for neoplasia in KTRs take into account: · Screening should be similar to the general population for cervical, breast, colon and prostate cancer (2C) · Screening is not recommended for renal cell carcinoma (2C) · Patient education pre and post transplantation (1C) · Patients should be aware of malignancy risk and encouraged to report symptoms which may represent de novo malignancy (e.g. breast or testicular lumps) (2D) · Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant (2C) · Patients with cirrhosis should undergo an annual hepatic ultrasound and determination of serum alpha fetoprotein (2C) b) KTR: Non-melanoma skin cancer (NMSC) · We recommend that KTRs should be educated about the adverse effects of sun exposure (1C) c) KTR: Non-melanoma skin cancer · We suggest that KTRs that an individualised assessment of hazard should be made according to risk factors (2C) · We recommend that patients should be encouraged to cover their skin in direct sunlight and to use total sunblock (Sun Protection Factor ≥50) (1D) · We suggest that self-examination should be encouraged with guidance provided. This should be supplemented by at least biannual review by a trained healthcare professional up to 5 years post-transplant and annual review from 5 years (2C) · We suggest that the prescription of acitretin as chemoprophylaxis be considered in those with ≥2 previous NMSC if there are no contraindications (2B) KTR: Immunosuppression in cancers
· We suggest that immunosuppression should be reduced if neoplasia develops (2C)
· We suggest that mammalian target of rapamycin inhibitors (m-TORi) are considered as alternative immunosuppressive agents in KTRs who develop de novo malignancy (2C)
· Kaposi sarcoma: We suggest that m-TORs have specific anti-tumour effects in Kaposi sarcoma (2C) KTR:Infection Complications a) Vaccination;We recommend that KTRs: · Should be vaccinated with inactivated viruses as per the normal population (1D) · Should receive annual influenza vaccination unless contraindicated (1C) · Should have hepatitis B surface antibody (HBsAb) levels rechecked annually and be revaccinated if antibody titres fall below 10 mIU/mL (2D) · Should not receive live attenuated vaccines (2C) · Should receive pneumococcal vaccine and a booster every five years (2D) b) KTR: Cytomegalovirus (CMV) disease
Prophylaxis and treatment of CMV disease, we recommend:
· Prophylaxis should be continued for 3-6 months, until immunosuppression has been reduced to long-term maintenance level (1B)
· Treatment should be administered for 6 weeks after treatment with a TDA (1C)
· All transplant units should be able to measure CMV serological status and quantify viral load (2D)
· Donor and recipient CMV status should be recorded at the time of transplantation (2D)
· Each unit should have a written protocolised CMV strategy based on prophylaxis or pre-emptive therapy (2D)
· For the treatment of mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are of equivalent efficacy (2C)
· The first line treatment of life-threatening CMV disease is intravenous ganciclovir (2D)
· Treatment duration should be determined by monitoring viral load (2C) c) KTR: Epstein Barr Virus (EBV) infection · We recommend that immunosuppression should be reduced or stopped following the development of post transplant lymphoproliferative disease (PTLD) (1C) · We suggest: a. Both donor and recipient should have their EBV serology recorded at the time of transplantation (2D) b. All high risk (D+/R-) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year (2C) c. EBV viral load should be monitored after the treatment of rejection (2C) d. Total immunosuppression should be reduced when EBV titres rise significantly (2C) d) KTR: Varicella Zoster Virus (VZV)infection
We recommend:
· Primary infection (chickenpox) should be treated with intravenous aciclovir or oral valaciclovir until the lesions scab over (1C)
· Uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over (1D)
· Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with intravenous aciclovir until the lesions scab over, together with a reduction in immunosuppression (1B)
· Varicella-susceptible KTRs (i.e. VZV IgG negative) with primary exposure to VZV should receive intravenous immunoglobulin, ideally within 96 hours, but up to a maximum of 10 days following exposure. If unavailable or after 10 days, oral aciclovir should be prescribed for seven days (1D)
· We suggest:
a. Patients on the waiting list who are VZV IgG negative should be vaccinated prior to transplantation (2D)
b. Immunosuppression should be reduced during primary infection (2D) e) KTR: Herpes Simplex Virus (HSV) infection
We recommend:
· Superficial HSV infection should be treated with appropriate oral agents until the lesions have resolved (1D)
· Systemic HSV infections should be treated with intravenous aciclovir and a reduction in immunosuppression until a response occurs and oral medication should be continued for at least 14 days (1C)
· We suggest that KTRs suffering frequent recurrent HSV infection should consider oral prophylaxis (2D) f) KTR: BK virus (BKV) nephropathy
· We recommend that confirmed BK nephropathy should be treated by reduction in immunosuppression (1D)
· We suggest:
a. Screening should also be carried out when renal function deteriorates in an unexplained fashion (2D)
b. KTRs should be screened for BKV viral load or by performing urine microscopy for decoy cells or by polymerase chain reaction (PCR) on urine or serum (2C)
c. Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40. Two cores containing medullary tissue should ideally be examined (2D)
d. Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml (2C)
e. There is no established specific treatment for BK nephropathy (2D)
g) KTR: Pneumocystis jirovecii infection – treatment and prophylaxis
We suggest: · All patients with confirmation (microscopy or PCR) of Pneumocystis jirovecii in respiratory secretions should be treated for 14 to 21 days with co-trimoxazole orally or intravenously (15-20mg/kg in three or four divided doses) (2B) · Patients with contraindications to treatment with co-trimoxazole should receive pentamidine (4mg/kg/day intravenously) (2B) · Adjunctive glucocorticoid therapy may be considered in patients with severe disease (2D) · KTR: Pneumocystis jirovecii infection; for post-transplant infection prophylaxis, we suggest: a. All patients should receive 3-6 months of treatment with co-trimoxazole 480 mg daily (1B) b. Oral antifungal prophylaxis should be administered for one week after transplantation (2C) c. In selected patients, prophylaxis against mycobacterium tuberculosis with daily isoniazid (supplemented with pyridoxine) should be instituted for six months after transplantation (2C) h) KTR: Hepatitis E Virus (HEV) · We recommend that Hepatitis E Virus (HEV)-screened blood components should be given to all KTR (1C)
KTR:Bone and JointDisease a. KTR: Osteoporosis; We suggest: · KTRs suffering from osteoporosis or at high potential risk should be considered for steroid-avoiding immunosuppression (2D) · KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2 (2D) · Treatment should be according to the Royal College of Physicians (RCP) guidelines for steroid-induced osteoporosis (2D) b. KTR: Tertiary hyperparathyroidism
· Severe hyperparathyroidism should be treated prior to transplantation (2D) · Cinacalcet can be used in KTR (2C) · Treatment should be the same as for other patients with CKD (2D) c. KTR: Gout
· We recommend that neither allopurinol nor febuxostat should be administered with azathioprine (1C)
· We suggest:
a. Hyperuricaemia should be treated when associated with gout, tophi or uric acid stones (2D)
b. Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided in KTRs (2D)
c. Acute gout may be treated with brief a course of oral prednisolone. (2D)
d. Colchicine is an effective treatment for gout in KTR (2D) d. KTR: Calcineurin inhibitor bone pain
We suggest:
· Reduction or withdrawal of CNIs should be considered in KTRs with intractable bone pain (2D)
· Dihydropyridine calcium antagonists also may be beneficial (2D)
KTR: Haematological Complications a) Anaemia
· We suggest that chronic anaemia should be managed in the same way as other patients with CKD (2D) b) polycythemia
· We recommend that initial treatment should be with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) (1C)
· We suggest:
a. Haemoglobin levels should be monitored at every clinic visit (2D)
b. Treatment should be initiated if the haematocrit or packed cell volume exceeds 52% in men and 49% in women (2D)
c. Venesection may be used in refractory cases.(2D) KTR: Reproductive Issues a) KTR: Conception and contraception (female) KTR:
· We recommend that MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately (1A)
· We suggest:
a. KTRs should wait for one year after transplant and have stable function before attempting conception (2C)
b. Counselling regarding fertility and reproduction should be offered to female KTRs and their partners either prior to transplantation or soon afterwards (2D)
c. m-TORi should be stopped prior to conception and replaced as appropriate (2D)
d. Pregnancy should be jointly managed with an Obstetrics department with experience of care of KTR (2D)
e. KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth of the baby unless there are contraindications (2C)
f. The risks and benefits of breastfeeding should be discussed (2D)
g. Contraception advice should be similar to the general population (2D) b) Conception and contraception (male)
We recommend: · Male KTRs are advised that MPA containing compounds have theoretical teratogenic potential in men taking these agents (1D) · KTRs should be advised that m-TORi reduce the male sperm count and counselled accordingly. (1C) · We suggest: a. All immunosuppressive drugs other than m-TORi can be used in male KTRs. Advice for MPA is as Guideline 11.3 (2D) b. The decision to continue MPA containing compounds in a male KTR wishing to conceive should balance the risk of theoretical teratogenicity against the risk of rejection on changing from MPA to azathioprine (2D) c. Men on m-TORi who wish to conceive should discontinue these agents prior to conception and replace them as appropriate (2D) d. Men who wish to maintain fertility should avoid m-TORi or bank sperm prior to starting these drugs (2D)
c) KTR: Sexual dysfunction We suggest: · Specific enquiry should be made regarding sexual dysfunction, preferably at an annual review clinic (2D) · Care pathways for dealing with sexual dysfunction should be established (2D) · Close liaison with local andrology service is recommended (2D) · Sildenafil is safe and effective in male KTR not taking nitrates (2D)
What is the evidence provided by this article?
This is a clinical practice guidelines.
Level of evidence grade 1.
Mohamed Saad
2 years ago
Clinical Practice Guidelines for the Post-Operative Care of the Kidney Transplant Recipient.
Final Version February 2017
Review Date February 2022 1-Clinic infrastructure.
The place dedicated for transplant recipient follow up, should be in outpatient area with consultant-level health care professional supervision, blood test results should be available and reviewed within 24 hours .
2-Clinic frequency.
uncomplicated patients may be reviewed progressively less frequently
2-3 times weekly for the first month after transplantation.
1-2 times weekly for months 2-3.
Every 2-4 weeks for months 4-6.
Every 4-6 weeks for months 6-12.
3-6 monthly thereafter.
3-Patient access.
All patients should have access for their labs results, access for inquires and information should be available in both written and electronic formats.
4-Recognising non-adherence.
Should prevent and detect non-adherence in kidney transplant recipients by determine factors of non-adherence and should establish Pathways should be in place for pediatric KTRs in transition and for adolescent KTRs.
5-immunosuppression regimen.
Our plan should be discussed with the recipient and decisions around selection of induction agent and maintenance immunosuppression. A-Induction therapy.
Should be started before or at the time of renal transplantation and interleukin-2 receptor antagonist (IL2-RA) for lower immunological risk and T-cell (lymphocyte) depleting antibodies for higher immunological risks and can be used also with lower immunological risks with the intention of
either steroid or calcineurin inhibitor (CNI) avoidance, not to delay CNIs till graft become functioning .
B-Maintenance immunosuppression.
=For patients who are low and medium immunological risk and are not at high risk of developing post transplant diabetes mellitus (PTDM) start tacrolimus with low trough level 4-8, mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception.
=Pt who complain of side effects related to tacrolimus peak dose toxicity, the slow release tacrolimus is indicated.
=Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients. Monitoring of immunosuppression.
We should monitor tacrolimus, cyclosporine and sirolimus by before the dose or after the dose as in cyclosporine C2, and should be available within 24 hours in the first 3 months. Acute rejection.
=16 gauge automated core biopsy needle used to bring 2 cores and biopsy better to be done before treatment unless there is a significant risk to the patient.
=We recommend that a protocol transplant renal biopsy be considered in the setting of persisting delayed graft function.
=We recommend that routine C4d and SV40 staining and send blood sample for (HLA)-specific antibodies. Treatment of acute rejection.
=High dose intravenous corticosteroids should be the first line treatment for acute cellular rejection and treatment of borderline rejection, maintenance steroids should be added or restarted in steroid-free patients.
=For refractory acute cellular rejection or aggressive vascular cellular rejection, lymphocyte depleting agents might be considered.
=Antibody mediated rejection (AMR) should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or Bortezomib. Chronic Allograft Injury.
=To diagnose CAI , we should serially follow up serum creatinine and urine PCR , and if suspected, renal biopsy should be done and be stained for C4d and SV40, and send blood sample for HLA specific antibodies.
=If there is signs of immune injuries , intensification of immunosuppression is required .
=If there are signs of chronic CNI toxicity , withdrawal is recommended. Renal biopsy in chronic allograft injury.
If there is a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection (BPAR) .
Every 7-10 days during delayed graft function (DGF) (2C)
If expected renal function is not achieved within 4-8 weeks (2D)
If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol). KTR: Hypertension.
-Strict F/U of BP and home measurement suggested and to keep target less than 140/90 mmHg and no specific type of anti-HTN medication preferred over the others .
-We should suspect RAS with resistant HTN specially in the first 3 months. KTR: Dyslipidemia.
Fasting lipid profile should be followed annually and treated as general population criteria , should keep in mind statin with CNI interaction, for example high dose simvastatin (≥40mg daily) should be avoided in conjunction with cyclosporine and/calcium channel antagonists. KTR: Diabetes mellitus.
=Screening by dipstick urinalysis and measurement of blood sugar level at each clinic visit, the diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing .
Screening for diabetic complications (retinal screening, foot care, neuropathy) in line with guidelines for non KTR patients with diabetes . KTR: Ischaemic heart disease.
We suggest that KTRs receive standard treatment for ischaemic heart disease, including thrombolysis, revascularization, and secondary prevention and smoking should be strongly discouraged. KTR: Screening for cancer.
-For cervical, breast, colon and prostate cancer, patients should be aware of malignancy risk and encouraged to report symptoms which may represent de novo malignancy (e.g. breast or testicular lumps) and Skin surveillance by a healthcare professional should be done every year, 5years after KTX. KTR: Non-melanoma skin cancer (NMSC).
=Pt should be educated about side effects of direct exposure to sunlight and importance of sun block use.
=Immunosuppression should be reduced if neoplasia develops .
=Mammalian target of rapamycin inhibitors (m-TORi) are considered as alternative immunosuppressive agents in KTRs who develop de novo malignancy, specially with Kaposi sarcoma. KTR: Vaccination.
Suggest to give all inactive vaccination as normal population and Should not receive live attenuated vaccines, annual influenza vaccine, pneumococcal vaccine and a booster every five years and f/u HBV s ab annually and booster dose according to titer. KTR: Cytomegalovirus (CMV) disease.
Prophylaxis should be continued for 3-6 months and Treatment should be administered for 6 weeks after treatment with a TDA.
For the treatment of mild and moderate CMV disease, oral Val ganciclovir or intravenous ganciclovir.
The first line treatment of life-threatening CMV disease is intravenous ganciclovir and treatment duration should be determined by monitoring viral load. KTR: Epstein Barr Virus (EBV) infection.
Immunosuppression should be reduced or stopped following the development of post transplant lymphoproliferative disease (PTLD).
EBV viral load should be monitored after the treatment of rejection. KTR: Varicella Zoster Virus (VZV) infection.
Primary infection (chickenpox) should be treated with intravenous acyclovir or oral valaciclovir and uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over and disseminated (>2 dermatomes), ocular or invasive shingles should be treated with intravenous acyclovir with reduction of immunosuppression.
KTRs who is VZV IgG negative and exposed to diseased person should receive intravenous immunoglobulin, ideally within 96 hours, but up to a maximum of 10 days . If unavailable or after 10 days, oral acyclovir should be prescribed for seven days. KTR: BK virus (BKV) nephropathy.
Immunosuppression should be reduced once diagnosed with serum BKV load exceeds 104 copies/ml, screening is important by serum or urine PCR or urine decoy cell in urine, BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40.
BK nephropathy diagnosed in an earlier graft is considered not contraindication for re-transplant. KTR: Pneumocystis jirovecii infection – treatment and prophylaxis.
Treated for 14 to 21 days with co-trimoxazole orally or intravenously and if contraindicated pentamidine is used. KTR: Post-transplant infection prophylaxis.
All patients should receive 3-6 months of treatment with co-trimoxazole 480 mg daily .
Oral antifungal prophylaxis should be administered for one week after transplantation. KTR: Osteoporosis.
Steroid free protocol for high risk patient and better to undergo DEXA scanning if eGFR >30 mL/min/1.73m. KTR: Tertiary hyperparathyroidism.
Severe hyperparathyroidism should be treated prior to transplantation and treatment should be the same as for other patients with CKD. KTR: Gout.
Hyperuricemia associated with gout , tophi or stone should be treated with steroid and or colchicine, NSAID should be avoided and neither allopurinol nor febuxostat should be administered with azathioprine. KTR: Calcineurin inhibitor bone pain.
Reduction or withdrawal of CNIs should be considered in KTRs with intractable bone pain and dihydropyridine calcium antagonists also may be beneficial. KTR: Polycythaemia.
ACEI or ARBs is the first line of treatment and venesection can be used in refractory cases. KTR: Conception and contraception (female).
MPA-containing immunosuppressant drugs & m-TORi should be stopped prior to conception and replaced appropriately.
Counselling both partners about Fertility and reproduction , should be planned with special criteria (stable normal function test for one year post KTX) with MDT follow up.
Aspirin decrease pre-eclampsia incidence , starting from 12 weeks gestation until birth. KTR: Conception and contraception (male).
All immunosuppressive drugs other than m-TORi can be used in male KTRs because it lead to low sperm count and decision to continue MPA containing compounds in a male KTR wishing to conceive should balance the risk of theoretical teratogenicity against the risk of rejection on changing from MPA to azathioprine.
Men who wish to maintain fertility should avoid m-TORi or bank sperm prior to starting these drugs .
Level of evidence V
mai shawky
2 years ago
Club 7; post operative care in KT Summary
· Consultant level medical professional must be present in each OPC.
· Follow up lab should be reviewed within 24 h, trough levels of CNI should be adjusted.
· Frequency of follow up: 2-3 times weekly for the first month, then 1-2 times weekly for months 2-3, then every 2-4 weeks for months 4-6, then every 4-6 weeks for months 6-12 and 3-6 monthly thereafter.
· Brand form of drugs should be used, generic immunosuppression compounds should not be used unless they have been shown to be bioequivalent and approved by the European Agency for the Evaluation of Medicinal Products.
· Never shift between formulations without appropriate supervision, and those patients should be closely monitored after switching between generic preparations until a new steady state is established.
· Induction therapyincludes anti IL 2 Rc antibodies in case of low immunological risk, and ATG in high immunological risk.
· Maintenance therapyincludes CNI, MMF and steroids.
· Azathioprine is used instead of MMF in case of pregnancy, lactation, fertile patient,unwilling to receive MMF.
· CNI is used life long, while steroids can be maintained on very low dose (5 mg/day).
· Diagnosis of acute rejection should be biopsy based (require 2 cores of renal tissue), without delay in starting treatment.
· Biopsy needed to be graded according to Banff classification.
· Routine staining with C4d and SV40 is needed to exclude other causes of acute graft dysfunction.
· Serum testing for DSA is needed together with biopsy.
· Treatment of acute rejection:
o Borderline acute cellular rejection should be treated
o High dose pulse steroids is 1st line in ttt of acute CMR.
o ATG is used in refractory acute cellular rejection or in vascular injury (Banff Type II and III) .
o Adjustment of maintenance therapy (increase CNI dose to achieve trough level) or restart steroids after its withdrawal or add it in steroid free regimens or shift from azathioprine to MMF or increase dose of MMF.
o ABMR can be treated by any of the following: IVIg; anti-CD20 antibody (rituximab), lymphocyte-depleting antibody (ATG) or bortezomib.
· Follow up of blood pressure and proteinuria (Presence of proteinuria by dipstick, should be quantified by spot ACR or PCR).
· Renal biopsy is the most important tool in case of unidentified cause of graft dysfunction (chronic allograft dysfunction).
· Management of chronic graft dysfunction:
o Decrease CNI (if evidence of toxicity).
o Increase immunosuppression if any evidence of immune mediated graft damage.
o Supportive measures as in CKD patients.
· Control of dyslipidemia and statin used to minimize cardiovascular morbidity and mortality.
· Indications of graft biopsy in chronic allograft injury:
o persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection.
o (Every 7-10 days during delayed graft function (DGF)
o If expected renal function is not achieved within 4-8 weeks
o Sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol).
· Management of hypertension;
o Measure ABP at office and ambulatory blood pressure measurement may be needed,
o No consensus about best antihypertensive drug, ACEis are preferred due added antiprotinuric effect (However, must be used with caution in the first 3 months post-transplant).
o Renal artery stenosis should be treated to control hypertension.
· Management of dyslipidemia:
o Fasting blood lipid should be measured annually.
o Control of its level as in general population to reduce risk of astherosclerosis.
o Statin is 1st line, however, caution should be taken as high dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/CCB.
· Management of diabetes mellitus:
o Is related to steroids and tacrolimus use.
o Diagnosis according to standards of DM (fasting> 126 mg/dl, post prandial >180 mg/dl, random glucose > 200 mg/dl, HBA1c > 6.5 ).
o Screening of complications (fundus for retinopathy, microalbumin for nephropathy)
· Management of ischemic heart disease:
o Treatment either thrombolytic therapy or revasculaization.
· Vaccination;
o Should be vaccinated upto date.
o Annual influenza vaccine is indicated, and receive pneumococcal vaccine and a booster every five years.
o Annual check of hepatitis B surface antibody (HBsAb) levels and be revaccinated if antibody titres fall below 10 mIU/mL
o Should not receive live attenuated vaccines.
· CMV prophylaxis and treatment:
o Prophylaxis for 3-6 months, until immunosuppression has been reduced to maintenance level.
o Monitoring of serology status and viral load should be available.
o In treatment mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are of equivalent efficacy. However, in life-threatening CMV disease intravenous ganciclovir is indicated.
o Treatment duration according to the viral load.
· BK nephropathy prophylaxis and treatment:
o Should be suspected in any case of acute graft dysfunction, screening by urine microscopy for decoy cells or by PCR on urine or serum.
o Confirmation by renal biopsy (2 cores involving medullary tissues and stain with SV 40) .
o If PCR revealed BKV load exceeds 104 copies/ml…reduction of immunosuppression therapy is indicated (no specific therapy for BK virus).
· Pnumocysis jirovecii prophylaxis and treatment:
§ co-trimoxazole 480mg daily for 3-6 months.
Level of evidence; V (consensus guidelines)
Doaa Elwasly
2 years ago
Guide lines of postoperative care in kidney transplant recipients
o Outpatient follow up organisation
· KTR infrastructure follow up includes
Availability of a consultant in a dedicated outpatient area having an access to rapid lab results within 24 h also with rapid access to MDT when needed ,the principles of treatment need to be planned according to the National Service Framework and Kidney Health Delivering Excellence
· Clinic frequency
Uncomplicated cases can be followed less frequently .
First month post transplantation follow up can be for 2-3 times weekly
2-3months could be 1-2 times weekly
4-6 months can be every 2-4 weeks
6-12 months can be every 4-6 weeks
then it can be 3-6 monthly. Patient need to have access to their data
· Chronic transplant care review
A detailed one need to be done annually postoperatively
o KTR non adherence
Factors leading to non adherence must be detected accompanied with early intervention
Children and adolescent pathways need to be clear.
o KTR immunosuppressive therapy KTR: immunosuppression regimen
The patient need to be involved in the choice of immunosuppression induction and maintenance. KTR: Induction immunosuppression
Immunosuppression started before or at the time of renal transplantation.
All cases must receive induction therapy which is IL2-RA in low immunological risk and T cell depleting antibodies for high immunological risk or when steroids and CNI are avoided.
KTR: Maintenance immunosuppression
Ø CNI is adviced to be started at transplantation time.
Ø For low immunological risk, CNI and antiproliferative agents with or without steroids .
Ø Low medium dose Tac can be used with steroids for cases at low risk of PTDM.
Ø Mycophenolic acid is the first-line anti-proliferative agent except in fertile cases who doesnot want contraception ,azathioprine can be used.
Ø If Tac is untolerable , cyclosporine ,sirolimus , everolimus, or belatacept can be used.
Ø Myfortic and MMF are equivalent immunosuppressives
Ø For low immunological risk cases steroid avoidance or withdrawal can be the policy in the first week post transplantation.
Ø In uncomplicated RT after 3 months, minimum CNI target levels can be used without withdrawing it.
Ø Low doses of steroids can be continued if steroids is not withdrawn in the first month.
Ø Monitoring immunosuppressives is needed
Tac and ciclosporin should be monitored trice a week 1st week after trnasplanation
Tacrolimus is monitored by the C0 trough level, while ciclosporin either by trough
(C0) or 2-hour post dose (C2) level
Sirolimus need to be monitored by the C0 trough level
Ø Only generic agents approved by the European Agency for the Evaluation of Medicinal Products can be used.
o Acute rejection
Ø Renal biopsy is done before diagnosing acute rejection unless it will delay therapy
Ø 16 gauge automated core biopsy needle is used with 2 cores .
Ø Protocol transplant biopsy can also be needed while C4d and SV40 staining should be performed
Ø HLA have to be sent at the biopsy time.
Ø The first line of therapy of acute cellular rejection is intravenous corticosteroids then maintenance including steroids as well.
Ø For refractory acute cellular rejection lymphocytic depleting agent can be used.
Ø AMR treatment includes steroids; plasma exchange; IVIg ; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib.
Ø After rejection episode MPA-based immunosuppression need to be used.
o Chronic Allograft injury
-Early detection is mandatory for prompt intervention.
-serum creatinine and urine albumin creatinine ratio must be followed up in each visit.
– Renal biopsy stained for C4d and
SV40 is the best investigation for deterioration of renal function
It can be done 7-10 days during DGF or with new onset of protienuria
-HLA antibodies need to be sent at the biopsy time
– for the treatment if CNI toxicity is detected ,CNI has to be withdrawn ,with maximising immunosuppressive therapy if there is evidence of immune injury.
o KTR: Cardiovascular disease and lifestyle
§ HTN
-BP should be recorded each visit ,targeted <140/90 along with home ambulatory BP monitoring .
-RAS blockers are best for proteinuria but must be used carefully in the first 3 months .
-Renal atretery stenosis can be the cause of resistant HTN
§ Dyslipidemia
-Fasting lipids levels should be monitored twice per year
– Statin therapy is used to decrease cardiovascular risk in patients with primary or secondary risks
-High simvastatin doses must be avoided with ciclosporin and CCB
§ DM
-PTDM need to be screened for each visit
– Immunosuppressive choice must consider the DM development risk
-PTDM need to be diagnosed and treated according to a protocol.
– diabetic recipients need to undergo screening for DM complications
§ Ischemic heart disease
– Transplant recipients can receive standard IHD treatment
– Smoking must be discouraged in transplant recipients
§ Lifestyle
Maintaining healthy lifestyle measures is essential including healthy diet , targeted weight
Avoid alcohol and recreational drugs and over the counter drugs and herbs
§ Neoplasia
-screening for cancer
Must be similar to general population as cancer cervix , breast , colon ,prostate
Patient must be aware of malignancy risks and report suspicious symptoms
Skin surveillance and hepatic US ,alpha fetoprotein for cirrhotic cases
-Nonmelanoma skin cancer
Recipients must be oriented about the hazards of sun exposure, use sunblock with high SPF
Biannual assessment by a specialised physicion for 1st 5 years then annually
Acitretin is adviced as chemoprophylaxis for those with ≥2 previous NMSC
Immunosuppresion need to be reduced in such case and m TORI can be used for cases with denovo malignancy specially Kaposi sarcoma.
o Infection complications
– Vaccines
Inactivated viral vaccines is recommended in KTR as well as annual influenza vaccine
HBsAb titer follow up if decreased revaccination is needed
Avoid live attenuated vaccines
Pneumococcal vaccine /5y
-CMV disease
Viral load and CMV Ab need assessment for donor and recipient
Prophylaxis therapy for 3-6 months and treatment for 6 weeks after TDA therapy
IV ganciclovir for lifethreatening CMV infection and oral valganciclovir for moderate cases
– EBV disease
PTLD occurrence necessitate withdrawal or reduction of immunosuppression
Both donor and recipient must have the EBV serological level recorded , and for high risk cases EBV viral load needs monitoring as immunosuppression will be reduced with high EBV titers
-VZV infection
IV Aciclovir or oral valaciclovir is used for primary infection treatment until the lesions scab over
Oral acyclovir or valaciclovir can be used for uncomplicated shingles.
Invasive shingles or with ocular involvement need to be treated with IV acyclovir and reduction of immunosuppression
VZV IgG negative cases with primary exposure should receive IVIG best within 96 hours, but up to a maximum of 10 days after exposure.
VZV IgG negative cases need to be vaccinated before transplantation
-HSV infection
Superficial lesions can be treated with oral acyclovir while systemic can be treated with IV acyclovir till lesions resolve with reduction of immunosuppression and oral for 14 days
Oral prophylaxis can be given for cases with recurrent infection
-BKV nephropathy
Can be treated with immunosuppression reduction.
It is suspected with unexplained deterioration of renal function.
Diagnosed by renal biopsy stained with SV40 screened for by BKV viral load or by urine microscopy for decoy cells or by PCR on urine or serum.
– Pneumocystis jirovecii infection
Treated by oral or IV cotrimoxazole for 14-21 days or pentamidine if cotrimoxazole is contraindicated .
-Post transplant infection prophylaxis
co-trimoxazole 480 mg daily for 3-6 months daily
oral antifungal prophylaxis for 1 week after transplantation
for certain cases TB prophylaxis with INH is needed for 6 months post transplantation
-HEV
Screening should be done
o Bone and joint disease
-Osteoprosis
DEXA scan can be done if e GFR >30 ml/min/1.73m2
Steroid free immunosuppressive regimens
better be applied in cases with or at high risk of osteoporosis.
Treated according to RTP guidelines for steroid induced osteoporosis
– Tertiary hyperparathyroidism
Severe cases need to be treated before transplantation as in CKD cases
– Gout
Avoid using allopurinol or febuxostat with azathioprine
Avoid NSAID
Acute gout can be treated with oral prednisolone course
Colchicine is effective in gout in KTR
– Calcineurin inhibitor bone pain
CNI better avoided
Dihydropyridine calcium antagonists can be used
o Hematological complications
-Anemia
Have to be manged as CKD cases
-Polycythemia
Initially treated with ACEI or ARBs
Treatment is according to hematocrit and PCV
Venesection is used in refractory cases
o Reproductive issues
-Conception and contraception in females
MPA drugs , m TORI need to be stopped before conception.
Conception can be possible after 1 year of transplant with stable kidney function
Fertility counselling is mandatory before transplantation as well as breast feeding counselling after delivery
Contraception counselling as general population
KTRs need to take aspirin 75 mg daily from 12 weeks gestation to decrease pre-eclampsia risk
– Conception and contraception in male
m TOR I is the only immunosuppressive that need to be avoided in males otherwise they can bank their sperms before starting the drug
MPA use have to balance risk against benefit
– Sexual dysfunction has to be treated with access to local andrology services Audit measures details for the Post-operative Care of the Kidney Transplant Recipient must be recorded
Rationale for Clinical Practice Guidelines for Post-Operative Care of the Kidney Transplant Recipient
Infrastructure need to be in place for KTR follow up in a standardized organised manner with easy accessibility
-level of evidence is V
KAMAL YOUSIF ELGORASHI ADAM
2 years ago
Summary of the Article; Introduction;
This Article is concerning to guide health care professional, specially those not expert, to care about transplant recipients, who sometimes doing their regular followup remote away from transplant center.
Also the Article follow the evolving in transplant medication to guide nephrologist who look after the transplant recipients.
It also cover the transplant time ; early post operative period and late phase of followup.
Other guidelines has been published in this guidelines and refference made to them.
Modified grading system used and classify strong recommondation as G1 and weak as G2, and the grade of each evidence was graded (A, B, C, D) as high, moderate, low, and very low respectively.
Guidelines;
kidney transpalnt recipient; Organizatin of outpatient follow-up, guidelines; We suggest the following infrastructures should be in place; @ A consultant level should be available in each transplant clinic. @ KTR should be reviewed in a dedicated outpatient area. @ A results of blood tests should be available within 24 hours. @ Result should be reviewed within 24 Hrs. @ there should be access to multidisiplinary team. @ Patient care should be planned along Principles set out in the National Service Frame Work. @ Clinic frequency; 2-3 time weekly fir the first month. 1-2 T/W for month 2-3. Every 2-4 weeks for month 4-6. Every 4-6 weeks for month 6-12. 3-6 month there after. @ option for online access should be available for all recipients, and for renal outpatient services, and all information should be available in written and electronic form. @ Annual detailed review, and should take over all recipient concern.
Kidney transplant recipient; Non-adherence Guidelines; # Identified all factors related to non-adherence. # pathway should be established for high risk condition. # Pathway should be in place for transition from pediatrics and for adolescence.
Kidney transplant recipient; immunosuppressant treatment Guidelines; & Immunosuppressants should be started before or at surgery. & Induction therapy should be applied for all recipients, (IL2-RA for low risk) and (TDAs for high risk). & TDAs also useful in low risk recipient when either steroid or CNIs intended to be avoided. & CNIs should be started at the time f surgery. & Maintenance immunosuppressants should always consist of CNIs/Antiproliferative agents/+/- steroids in a low to moderate risk recipients. & Low-medium dose of TAC should be given to low- to moderate immunological risk recipients with steroid, and are not at high risk for NODAT. & MMF should be the first line in preference to azathioprine, except in fertile KTR, who are unwilling to conceive. & Slow release TAC should be an option in cases of intolerance to side effect. & TAC intolerant recipients can be shifted to CyA, SIR, EVr, or balatacept. & MMF and enteric-coated MyFortic provide equivalent immunosuppression. & Steroid avoidance or withdrawal can be in the first week of transplantation in low risk recipients. & Minimum target level in uncomplicated renal transplant after 3 month. & CNIs should not be withdrawn. & Steroid if not withdrawn during the first month, should be continued with minimum dose 5 mg OD or less. & TAC and CyA level should be monitored, Initially (3times a week), TAC monitored at C0, while CyA at C0, C2. & SIR monitored at C0. & generic Immunosuppressants should not be used unless approved by EAEMP. & KTRs should be aware of existance of generic product and not shift to them unless under supervision. & Drugs should be prescribed in a brand name. & KTRs should be closely monitored when shifting between drug brands untill steady state is established.
Kidney transplant recipient; acute rejection Guidelines; * Biopsy should be carried out before treating acute rejection, unless it will delay treatment or carry a hazard to patient. * 2 core should be taken for biopsy, since it will increase the sensitivity. * 16 gauge automated core biopsy needle should be used. * Protocol biopsy should be carried out in the setting of persisting DGF. * Routine C4d and SV40 staining should be performed to address other causes of rejection. * Serum sample for HLA antibodies at time of biopsy. * Border line acute cellular rejection should be treated in the setting of acute graft dysfunction. * High dose IV corticosteroid should be commenced in case of acute cellular rejection. * Maintenance steroid should be started in steroid free regiment recipients if they develop acute rejection of any type. * LDA should be considered in refractory cellular rejection or in aggressive vascular cellular rejection. * AMR should be treated with one of the following (Steroid/PE/IVIG/ antiCD20 antibodies, LDAs, or Bortezumib). * Acute rejection, (unless ass with CNI level ), azathioprine should be sustituted with MMF, or exciting dose to be maximized.
Kidney transplant recipient; Chronic Allograft injury Guidelines; @ Renal function should be tested for each visit to detect allograft injury. @ Renal biopsy is the optimum way for parynchymal graft dysfunction where the cause is uncertain. @ Renal biopsy with chronic deteriorating renal function should be stained with C4d, and SV40. @ Serum sample should be taken with the time of biopsy for HLA antibodies. @ Chronic allograft injury should be treated with; (withdrwal of CNIs, in tixicity, non-specific IFTA), (intensification of immunosuppressants in cellualr rejection or humoral rejection). @ Following the same strategy of preventive measures as CKD patients. @ Graft biopsy indicated if; (Persistent incresae in Cr or failure to return back to base line in biopsy proven acute rejection), (Every 7-10 days during DGF), (If expected renal function not acheived during 4-8 weeks), (If sustained new onset proteinuria).
KTR ; Cardiovascular disease and lifestyle Guidelines; # BP should be recorded in each visit. # clinic BP should be <140/90 and < 130/80 if PCR > 50 or ACR > 35. # No evidence on superiority over AHM over the other, so target should be on absolute BP control rather than the use of individual agent. # RAAS inhibitors are more effective in reducing proteinuria, but caution should be taken if used in the first 3 month. # persistent HTN should be investigated as RAS may be the cause. # Resistant HTN may be due to transplant RAS, and should be investigated according to local practice. # Fasting lipid profile should be invesigated annually. # treatment as same as general population. # KTRs with cardiovascular rsik receive statins to reduce risk of CAD. # The choice and dose should take into account concurrent immunosuppressants, with dose simvastastin be avoided in conjunction with Cic and Ca channel antagonists. # Screening of development of PTDM by urine dipstick and serum blood glucose. # Post Tx immunosuppressant should take into account risk of diabetes development. # The diagnosis of PTDM based on WHO criteria. # PTDM stablished once immunosuppressant started. # PTDM managed with collaboration with specialist in DM. # All unit should have protocol treatment of DM. # KTR should be screened for diabetes complicationi in line with guidelines for non- KTR patient with DM. # KTR should receive standard treatment for IHD, including thrombolysis, revascularization, and secondary prevention. # Smoking should be strongly discouraged in KTR. # Maintenance of healthy diet should be eencouraged. # An Ideal weight should be targeted BMI </ 25 kg/m2. # Weight measurement services should be available. # KTR should underwent physical activity, similar to that recommended to age and comorbidity. # Alcohol consumption should be within national guidelines. # Recreational drug should be avoided. # the use of over-the-counter medication (herbal medicine) should be discouraged
KTR ; Neoplasia Guidelines; & Screening should be similar to general population for cervical, breast, colon and prostate. & Screening not recommended for RCC. & Recipient should be aware of malignancy risk, and encourage to report symptoms of malignancy. & Skin survalence at least biannually for 5 years and anually after 5 years. & Patient with cirrhosis should undergo an annual US and alpha feto protein. & KRT should be educated about the risk of sun exposure, and to cover their skin in direct sun exposure and to use sun protection. & Encourage self examination. & Chemoprophylaxis for those with >/ previous NMSC. & Immunosuppressant should be reduced if neoplasia developes. & mTORi should be considered if malignancy develop, and mTORi has specific antitumors activity against Kaposi sarcoma.
KTR ; Infection complications Guidelines; * KTR should be vaccinated by inactive viruses as per general population. * should receive annual influenza vaccination unless contraindicated. * Should have hepatitis B surface antibody levels rechecked annually, and be revaccinated if antibody titre < 10 mIU/ml. * should not receive live vaccines. * Should receive pneumococcal vaccine and booster every 5 years. * Prophylaxis against CMV should be continuous for 3-6 months, until immunosuppressant had been reduced to long term maintenance. * traetment should be continued for 6 weeks after treatment with a TDA. * All transplant centers should be able to measure serological ststus and to quantify viral load. * Donor and recipient CMV status shouldbe recorded at time of RT. * Each unit have a written CMV protocol. * Mild to moderate CMV disease oral or IV protocol are of same efficacy. * First line treatment of sever CMV disease is IV ganciclovir. * treatment duration should be monitored by viral load. * All donor and recipient they have their EBV serology before RT. * All high risk EBV recipient/donor should have EBV viral load. * EBV load should be monitored after treatment of acute rejection. * Total immunosuppressant should be reduced when EBV titre had significantly rising. * Primary infection with Chickenpox should treated with IV or oral aciclovir. * Uncomplicated shingles treated with oral or valaciclovir . * Dissiminated shingles , occular or invasive traeted with iv aciclovir, together with the reduction of immunosuppressants. * Varicella-susceptible KTRs should be treated with IVIG, idealy within 96 hours but up to maximum of 10 days, * Superficial HSV should be treated with oral agents until lesion resolved. * Systemic HSV should be treated with IV aciclovir and reduction of immunosuppressant until responce occur and oral agent should be started after at least 14 days. * Recurrent infection should considered oral prophylaxis. * BK nephropathy should be treated with reduction of immunosuppressants. * Screening should be done with unexplaned detrioration of renal function. * Screening should include viral load or decoy cell urine test, or PCR urine or serum. * BK nephropathy should be confirmed by biopsy stained with SV40. * BK viral load exceed 10)4 copies should reduce immunosuppressant. * No established specific treatent . * Re-transplantation should be considered in early graft infection.
KTR ; Bone and Joint disease Guidelines; $ Neither allopurinol or febuostat should be used with Azthioprine. $ Hyperuricemia should be treated when ass with gout, tophi, or uric acid stone. $ NSAID should be avoided in KTR. $ Acute gout be treated with short coarse of prednisolone. $ Intractable bone pain can be treated with reduction of CNI dose. $ Dihydropyridine Ca antagonist also may be beneficial.
KTR ; hematological complication guidelines; @ Chronic anemia managed as same as CKD. @ In polycysthemia first managment should be ACE-i or ARB.
KTR ; Reproductive issues Guidelines; # MPA-should be stoped prior to conception, and replaced appropriately. # KTRs should wait for at least 1 year for stabilize renal function before conceive. # Councelling regarding fertility prior and post transplantation. # mTORi should be stopped prior conception and replace appropriately. # Pregnancy should be comanage with obstetrician. # Asprin 75 mg daily after 12 week gestation and until birth to minmize preeclampsia. # Risk and benefit of breast feeding should be counselled . # Male KTR are advice that MPA have teratogenic effects. # m TOR i reduce sperm count and councelled accordingly.
Level of evidence ((V))
Hadeel Badawi
2 years ago
These guidelines cover the period after renal transplantation, specifically from initial hospital discharge until graft failure or patient death.
The management of KTR can be divided into two phases:
a. Early post-operative phase when prevention of AR and opportunistic infection, optimization of graft function.
b. Later phase to preserve good graft function, ensure medication adherence, and prevent
the long-term consequences of IS – malignancy, infection and premature CVD.
Management of the early and late phase complications of transplantation requires monitoring at reducing the frequency, awareness of complications, access to the investigation, and strategies for preventing and treating complications.
KTR- Organization of Outpatient Follow-up: Clinic infrastructure:
-Consultants should be available for every clinic.
– Dedicated outpatient area
– Availability of results of blood tests within 24 hours
-Access to an MDT Clinic frequency:
2-3 times weekly for the first month after transplantation
1-2 times weekly for months 2-3
Every 2-4 weeks for months 4-6
Every 4-6 weeks for months 6-12
3-6 monthly after that Patient access:
-On-line access to their results
-Open access to outpatient service and established point of contact for enquiries
-Patient information should be available in both written and electronic formats Chronic transplant care review
-Detailed review should be performed annually post-operatively in parallel with a formal medical review.
Non-adherence Recognizing non-adherence
-Prevent and detect non-adherence, and factors associated in KTR.
-Established interventional pathway for nonadherence
Immunosuppressive treatment Induction immunosuppression
– IS drugs should be started before or at the time of KT to all KTRs, and their choice according to immunological risk either IL2-RA or T-cell depleting antibodies.
CNI should be started at the time of transplantation and not delayed until the graft is functioning Maintenance immunosuppression
-Normally consist of CNI, and anti-proliferative agent, +/- corticosteroids in low and medium risk KTR
-Tacrolimus (trough target 4-8 ng/mL) is recommended in low and medium risk and are not at high risk of PTDM.
– Anti-proliferative agent: MPA-based drugs should be the first-line in preference to azathioprine.
– Slow release tacrolimus for patients who suffer intolerable SE.
– If tacrolimus was not tolerated for SE to considere for the use of ciclosporin, sirolimus, everolimus, or belatacept
-MMF and enteric-coated MPA provides equivalent maintenance immunosuppression.
-Steroid avoidance or steroid withdrawal in low immunological KTR
– To aim for minimum target levels for CNIs after 3 months in uncomplicated renal transplantation
-CNIs should not be withdrawn.
-If steroids are not withdrawn to be continued at low dose (prednisolone 5 mg per day or less).
Monitoring of immunosuppression
-CNI level should be monitored, initially should be three times a week.
-Levels should be checked when adding new medication, change the dosage or in unexplained graft dysfunction
-Tacrolimus monitored by the trough (C0) level, while ciclosporin by either C0 or C2 level
– Result should be available within 24 hours
-The utility of monitoring MPA C0 levels is uncertain
– Sirolimus monitored by the C0 trough level
Prescribing and the use of generic agents
-Generic IS compounds should not be used
– KTRs should be aware about importance of not switching
-Drugs should be prescribed by brand name
-Closely monitored after switching between generic preparations until a new steady state is established.
Acute rejection Diagnosis of acute rejection
-Renal biopsy should be carried out before treating an AR unless this will delay treatment or pose a significant risk.
-Two cores of renal tissue should be obtained.
-Using16 gauge automated core biopsy needle recommended.
-Protocol transplant renal biopsy might be considered.
– Use of C4d and SV40 staining should be performed upon transplant biopsies
– At the time of renal biopsy send for HLA-specific antibodies. Treatment of acute rejection
-Borderline ACR should be treated in the context of acute graft dysfunction
-High dose IVMP should be the first line treatment for ACR
-Maintenance steroids should be added or restarted in steroid-free patients with ACR.
– lymphocyte depleting agents in refractory ACR or aggressive vascular CR
-AMR should be treated with steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting agent or bortezomib
-After an episode of rejection azathioprine should be switched to MPA-based IS, MPA should be started or maximized.
Chronic Allograft Injury Diagnosis of Chronic Allograft Injury
-Proactive and systematic approach should employed to manage graft dysfunction.
-Renal function should be monitored at each clinic visit by serum creatinine and PCR or ACR.
-Biopsy is the optimal investigation
-Biopsies should be stained for C4d and SV40
-At the time of renal biopsy to send for HLA-specific antibodies (2C) Treatment of chronic allograft injury
-CNI withdrawal if there is evidence of CNI toxicity or non-specific IFTA.
-Intensification of IS if there is evidence of ongoing immune injury. Renal biopsy in chronic allograft injury
-If there is a persistent unexplained elevation of creatinine or failure to return to baseline
– After an episode of biopsy proven acute rejection (BPAR)
-Every 7-10 days during DGF
-Renal function is not achieved within 4-8 weeks.
-New onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol).
Cardiovascular Disease and Lifestyle Hypertension
-BP should be recorded at each clinic visit.
-Clinic BP should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35)
– Home BP & ABPM lower BP targets <135/80mmHg
– Effort should be focused on achieving absolute BP control
– RAAS Inhibitors may be more effective in reducing proteinuria.
-Resistant HTN may be due to TRAS
Dyslipidemia
-Fasting lipid levels should be measured annually
– Target is the same as in the general population.
– Statin therapy to reduce the risk of CAD.
– High dose simvastatin (≥40mg daily) should be avoided in conjunction with CCB or ciclosporin.
Diabetes mellitus
-Screening for PTDM by dipstick urinalysis and BSL level at each clinic visit.
-Choozing IS should take into account risk for diabetes development
-PTDM diagnosis is made based on WHO criteria, once established on stable maintenance IS
-PTDM should be managed with specialists in diabetic medicine
-Screening for diabetic complications using guidelines for non KTR patients with diabetes Ischemic heart disease
-Standard treatment for IHD, including thrombolysis, revascularization, and secondary prevention. Smoking cessation
-Smoking should be strongly discouraged. Lifestyle measures
-Advice on healthy lifestyle; healthy diet, target ideal BW and BMI, physical activity, avoid alcohol and recreational drugs, discourage the use of OTC drugs.
Neoplasia Screening for cancer
-Screening should be similar to the general population for cervical, breast, colon and prostate cancer
-Screening is not recommended for RCC
-Patients should be aware of malignancy risk.
-Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant
-Patients with cirrhosis ;an annual hepatic US and AFP Non-melanoma skin cancer (NMSC)
-Educated about the adverse effects of sun exposure, to use total sunblock SPB ≥50.
-Encourage self-examination, and at least biannual by trained healthcare professional up to 5 years post-transplant and annual review from 5 years.
– Prescription of acitretin as chemoprophylaxis if ≥2 previous NMSC Immunosuppression in cancers
-IS should be reduced if neoplasia develops.
– m-TORi) are considered as alternative IS if developed de novo malignancy, also, have specific effects in Kaposi sarcoma
Infection Complications Vaccination
KTRs should be vaccinated with inactivated viruses, annual influenza vaccination unless contraindicated (
-HBsAb levels rechecked annually and be revaccinated if titres fall below 10 mIU/mL
-Should not receive LAV
-Pneumococcal vaccine and a booster every five years.
Cytomegalovirus (CMV) disease Prophylaxis and treatment of CMV disease
-Prophylaxis should be continued for 3-6 months, until IS has been reduced to maintenance level
-Treatment to be administered for 6 weeks after treatment with a TDA
-Donor and recipient CMV status should be recorded at the time of transplantation
-For mild and moderate CMV disease, oral valganciclovir and IV ganciclovir are of equivalent efficacy
-For life-threatening CMV disease IV ganciclovir recommended.
-Duration should be determined by monitoring viral load
Epstein Barr Virus (EBV) infection
-IS to be reduced or stopped following the development of PTLD.
-Both donor and recipient EBV serology should be recorded at the time of transplantation
-All high risk (D+/R-) should have EBV viral load measured immediately after transplantation, monthly for 6 months, and 3 monthly to one year.
– EBV viral load monitoring at time of rejection
-IS should be reduced when EBV titres rise significantly
Varicella Zoster Virus (VZV) infection
-Primary infection; treated with IV aciclovir or oral valaciclovir until the lesions scab over.
– Uncomplicated shingles; treated with oral acyclovir or valaciclovir until the lesions scab over
-Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with IV aciclovir until
with a reduction in IS.
-Varicella-susceptible KTRs with primary exposure to VZV should receive IVIG, If unavailable oral aciclovir
-VZV IgG negative should be vaccinated prior to transplantation
-IS should be reduced during primary infection
Herpes Simplex Virus (HSV) infection
-Superficial HSV infection; treated with oral agents
-Systemic HSV infections; treated with IV aciclovir and a reduction in IS
– Recurrent HSV infection; oral prophylaxis
BK virus (BKV) nephropathy
-Should be treated by reduction in IS.
-Screening when unexplained deterioration of renal function by viral load or by urine microscopy or PCR
– Suspicion to be confirmed by renal biopsy, including SV40 stain.
-IS should be reduced when the serum BKV load exceeds 104 copies/ml
Pneumocystis jirovecii infection – treatment and prophylaxis
-All confirmed cases should be treated for 14 to 21 days with co-trimoxazole orally or IV.
-Pentamidine if there is contraindications to co-trimoxazole.
– In severe disease consider glucocorticoid
-All KTR should receive 3-6 months co-trimoxazole 480mg daily for PCP prophylaxis
-Oral antifungal prophylaxis for one week after transplantation
– TB prophylaxis against with daily INH with pyridoxine for 6 months after transplantation in selected cases.
Hepatitis E Virus (HEV)
Screened blood components should be given to all KTR
Bone and Joint Disease Osteoporosis
-KTRs with osteoporosis to consider for steroid-avoiding IS
-KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2 .
-Treatment according to the RCP guidelines for steroid-induced osteoporosis Tertiary hyperparathyroidism
-Severe hyperparathyroidism should be treated prior to transplantation
– Cinacalcet can be used in KTR
-Treatment should be the same as for other patients with CKD Gout
– Neither allopurinol nor febuxostat should be administered with azathioprine
-Hyperuricaemia should be treated when associated with gout, tophi or uric acid stones
-NSAIDs) should be avoided in KTRs
-Acute gout; treated with brief a course of oral prednisolone.
-Colchicine is an effective treatment for gout in KTR Calcineurin inhibitor bone pain
-Reduction or withdrawal of CNIs when intractable bone pain.
-Dihydropyridine calcium antagonists also may be beneficial
Haematological Complications Anemia:
-Chronic anemia; managed as other patients with CKD Polycythemia
-Initial treatment ACEIs or ARBs.
-Treatment initiation if the Hct exceeds 52% in men and 49% in women
-Venesection may be used in refractory cases
Reproductive Issues Conception and contraception (female)
-MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately.
– m-TORi should be stopped prior to conception and replaced
– KTRs should wait for one year and have stable function before attempting conception
– KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth
-Contraception advice should be similar to the general population Conception and contraception (male)
MPA containing have theoretical teratogenic potential in men.
m-TORi reduce the male sperm count
All immunosuppressive drugs other than m-TORi can be used in male KTRs. Sexual dysfunction
-Care pathways for dealing with sexual dysfunction should be established
-Close liaison with local andrology service is recommended
– Sildenafil is safe and effective in male KTR not taking nitrates
Level 5
Mohamed Mohamed
2 years ago
VII. Post-Operative Care in the Kidney Transplant Recipient (BTS GUIDELINES- 2017) 1.Summarise this article These guidelines are useful to all those involved in the care of KTR who are non-experts, & to trainees (medical surgical), general practitioners, nurse specialists & others. The period covered is from KTX (initial discharge) until graft failure or patient death. KTR management phases: 1.Early post-op: involves prevention of AR & opportunistic infections, & optimizing graft function. 2.Later phase: to ensure good graft function, adherence to & prevention of long-term IS therapy effects (malignancy, infection & CVD) Management of complications of TX requires regular monitoring, awareness of complications, access to investigation, & strategies for prevention & treatment of complications.
The modified GRADE system was used in these guidelines. Summary of Post-Operative Care of the KTR 1. Outpatient Follow-up Clinic infrastructure
A consultant should be available
A dedicated outpatient area
Blood tests results available & reviewed within 24 hr
Access to a MDT (pharmacist, dietician, social worker & psychologist) Clinic frequency
Uncomplicated KTR reviewed progressively less frequently (2C) Patient access All KTRs should have an open access to support services & results. (2C) Chronic TX care review A detailed patient-centered review done annually post-op (2C) …………………………………….. 2.Non-adherence Recognize & prevent non-adherence in KTR. (2C) …………………………………….. 3.Immunosuppressive treatment Regimen
KTR &/or carer engaged in the selection of induction agent & maintenance IS (1D) Induction IS
IS drugs started before or at the time of KTX (1B)
Biological agents for all; IL2-RA (low immunological risk) or TDAs (higher risk) (1B)
TDAs for steroid or CNI avoidance regimen in lower risk KTRs (1C)
· CNI started at the time of TX & not delayed until the graft isfunctioning (2C) Maintenance IS
·Should consist of a CNI & an anti-proliferative agent +/- corticosteroids in low & medium risk KTRs (1B)
·Tac (trough 4-8 ng/mL) is the CNI of choice in KTRs also taking steroids who are low & medium immunological risk & are not at high risk of developing PTDM) (2C)
·MPA -based drugs are 1st-line anti-proliferative in preference to AZA, EXCEPT in fertile KTRs not willing to use reliable contraception (2B)
Slow release tac is an option for those intolerant to S/Es related to peak dose toxicity (2C)
·Use of 2nd-line agents (cycl, sirolimus, everolimus, or belatacept) considered for KTRs intolerant to tac or suffer serious S/E related to its use (1B)
·MMF& EC-MPA provide equivalent maintenance IS (2B)
·Steroid avoidance/withdrawal can be used during the 1st post-TX week in low risk KTRs (2B)
·Aim for minimum CNIs targets in uncomplicated KTRs after 3 months (2C)
·CNIs should not be withdrawn (2B)
·If steroids not withdrawn within 1stmonth, they should be continued at low dose (pred=/< 5 mg/ day) (2C) Monitoring of IS ·CNI levels should be monitored; initially 3 times a week. ·Check levels when any new medication is added, dosage or formulation is changed, or if unexplained graft dysfunction occur (2C) ·Tac monitored by trough (C0); cycl by either C0 or 2-hour post dose (C2) level (2C) ·Levels should be available within 24 hours in the 1st 3 months after TX (2D) ·Utility of monitoring MPA C0 levels is uncertain (2D) ·Sirolimus monitored by the C0 trough level (2C) Use of generic agents
·Should not be used unless bioequivalent & approved the EAEMP (2D)
·KTRs made aware of their existence & not to switch between preparations without supervision (2D)
·Drugs prescribed by brand name (2D)
·Close monitor after switching between generic preparations until a new steady state reached (2D) …………………………………….. 4. Acute rejection Diagnosis Biopsy before treating unless undue delay or significant risk to the patient (1C) 2 cores of renal tissue obtained at biopsy to increase the sensitivity (2C)
A 16 gauge automated needle is used where possible (1C)
A protocol biopsy in the setting of persisting DGF (1C)
Routine C4d & SV40 staining done on biopsies to address other causes of graft dysfunction (2C)
Sample sent at the time of renal biopsy (for graft dysfunction) for HLA-specific antibodies (2C) Treatment
Borderline ACR should be treated in the context of acute graft dysfunction (2D)
High dose IV corticosteroids is the 1st-line treatment for ACR (1D)
Maintenance steroids added or restarted in steroid-free patients undergoing AR (any type) (2D)
TDAs for refractory ACR or aggressive vascular cellular rejection (Banff 4 Type II & III) (2C)
AMR treated with =/> 1 of the following: steroids; PE; IVIG; anti-CD20 antibody, TDAs or bortezomib (2C)
BTS guidelines on Ab-incompatible TX for management of rejection in the context of Ab-incompatible TX (1A-D)
After rejection – AZA switched to MPA, MPA started, or dose of MPA maximized (2D) …………………………………….. 5.Chronic Allograft Injury Diagnosis Early detection to maximize the potential for intervention. A proactive & systematic approach to manage graft dysfunction (1C) Renal function monitored at each visit by assessment of creatinine & urine protein dipstick, followed by PCR or ACR if positive (2C)
Biopsy is the optimal test for parenchymal causes of graft dysfunction where the cause is uncertain (2C)
Biopsies should be stained for C4d & SV40 (2C)
HLA specific antibodies tested at the time of renal biopsy (for graft dysfunction) (2C) Treatment
Withdraw CNIs if evidence of toxicity or non-specific IF/TA (2C)
Intensify IS if ongoing immune injury (cellular rejection &/or humoral rejection) (2C)
Preventive strategies similar to other CKD patients (2D) Renal biopsy Is indicated:
If persistent unexplained rise of creat or failure to return to baseline after a BPAR (1C)
Every 7-10 days during DGF (2C)
If expected renal function is not achieved within 4-8 weeks (2D)
If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol) (2C) …………………………………….. 6. CVD & Lifestyle Hypertension
BP should be recorded at each visit (1C)
BP should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
Home BP recordings & 24-hour ambulatory recordings help in some instances but lower BP targets should then be set (<135/80mmHg) (2D)
No any antihypertensive agent is better than any other & effort focused on absolute BP control rather than the use of individual agents (2D)
Inhibitors of the RAS may be more effective in the minimisation of proteinuria but should be used with caution in the 1st3 months post-TX (2C)
Resistant HTN may be due to TX renal artery stenosis & investigated according to local practice (2D) Dyslipidaemia
Fasting lipid levels should be measured annually (2C)
Treatment targets same as in general population (2C)
KTRs at increased primary or secondary CV risk receive statin to reduce the risk of CAD (2C)
The choice & dose of statin should consider concurrent IS. High dose simvastatin (≥40mg daily) avoided in conjunction with Cycl &/ CCBs (2D) Diabetes mellitus
Screening for PTDM by dipstick urinalysis & blood sugar level at each visit (2C)
Post-TX IS should consider risk factors for the development of diabetes (2C)
Diagnosis of PTDM is based on WHO criteria for the diagnosis of DM based on fasting or random blood, HBA1c or OGTT (1C)
PTDM diagnosis is made once KTRs are established on stable maintenance IS (2D)
PTDM should be managed in collaboration with specialists in diabetic medicine (2D)
All units should have a protocol for the management of PTDM (2C)
KTR with diabetes (either prior to TX or PTDM) should be screened for diabetic complications in line with guidelines for non KTR patients with diabetes (2D) Ischaemic heart disease
KTRs should receive standard treatment, including thrombolysis, revascularisation, & secondary prevention (2C) Smoking cessation
Smoking should be strongly discouraged in KTRs (1A) Lifestyle measures
Advice on healthy lifestyle is a routine part of post-TX care:
Maintenance of a healthy diet encouraged (2C)
Ideal weight targeted (BMI ≤25 kg/m2) (2C)
Weight management services should be available (2C)
KTRs should participate in physical activity appropriate to age & comorbidity (2D)
Alcohol intake within national guidelines (2D)
Recreational drug avoided (2D)
OTC medications & herbal medicines discouraged (2D) …………………………………….. 7. Neoplasia Screening
Similar to general population for cervical, breast, colon & prostate cancer (2C)
Not recommended for RCC (2C)
Patient education pre & post-TX (1C)
KTRs should be aware of malignancy risk and encouraged to report symptoms (2D)
Skin surveillance biannually up to 5 years & annually from 5 years post-TX (2C)
Cirrhotic KTRs should have annual hepatic USS & alpha fetoprotein (2C) Non-melanoma skin cancer
KTRs educated about A/Es of sun exposure (1C)
Individualized assessment according to risk factors (2C)
KTRs encouraged to cover skin in direct sunlight & to use total sun-block (1D)
Self-examination encouraged with guidance provided (2C)
Acitretin as chemoprophylaxis for those with ≥2 previous NMSC (2B) Immunosuppression in cancers
IS reduced if neoplasia develops (2C)
m-TORi as alternative IS in KTRs who develop de novo malignancy (2C) Immunosuppression in KS
m-TORs have specific anti-tumour effects (2C) …………………………………….. 8. Infection Complications Vaccination
With inactivated viruses as in normal population (1D)
Annual influenza vaccination (1C) HBsAb rechecked annually & revaccinate if Ab titres fall < 10 mIU/mL (2D) Live attenuated vaccines not given (2C) Pneumococcal vaccine & a booster every 5 years (2D) Prophylaxis & treatment of CMV disease
Prophylaxis for 3-6 months (1B)
Treatment for 6 weeks after treatment with a TDA (1C)
Measure CMV serological status & quantify viral load (2D)
Donor & recipient status recorded at the time of TX (2D)
A written protocol based on prophylaxis or pre-emptive therapy (2D)
For mild & moderate disease, oral valganciclovir & IV ganciclovir are equivalent (2C)
IV ganciclovir is 1st choice in life-threatening disease (2D)
Treatment duration determined by monitoring viral load (2C) EBV infection IS reduced or stopped following PTLD (1C)
Serology recorded at the time of TX for donor & recipient (2D)
D+/R- KTRs: viral load checked immediate after TX, monthly for 6 mo, & monthly to 1 year (2C)
Viral load monitored after the treatment of rejection (2C)
IS reduced when titers rise significantly (2C) VZV infection
Chickenpox treated with IV aciclovir or oral valaciclovir (1C)
Uncomplicated shingles treated with oral acyclovir or valaciclovir (1D)
Disseminated, ocular or invasive shingles treated with IV aciclovir & reduce IS (1B)
Susceptible KTRs given IVIG (1D)
Patients on waiting list who are IgG -ve vaccinated prior to TX (2D)
IS reduced during primary infection (2D) HSV infection Superficial infection treated with oral agents (1D) Systemic infections treated with IV aciclovir & a reduction in IS (1C) BK nephropathy · Treated by reduction in IS (1D)
Screening if unexplained renal function deterioration (2D)
Screened for viral load or by urine microscopy for decoy cells or by PCR on urine or serum (2C)
Diagnosis confirmed by renal biopsy (stained for SV40) (2D)
IS reduced when BKV load > 104 copies/ml (2C)
No established specific treatment (2D)
Re-TX can be safe in those who have BK nephropathy in an earlier graft (2C) Pneumocystis jirovecii infection
Treated for 14 – 21 days with co-trimoxazole orally or IV (2B)
Pentamidine if contraindication co-trimoxazole (2B)
Adjunctive glucocorticoid in severe disease (2D) Post-transplant infection prophylaxis
3-6 months of co-trimoxazole 480 mg daily (1B)
Oral antifungal for 1 week after TX (2C)
Mycobacterium TB prophylaxis (daily INH for 6 months) in selected cases (2C) Hepatitis E Virus (HEV)
HEV-screened blood components given to all KTR (1C) …………………………………….. 9. Bone & Joint Disease Osteoporosis
Steroid-avoiding IS considered (2D)
DEXA scanning if eGFR >30 mL/min/1.73m2 (2D)
Treatment according to the RCP guidelines for steroid-induced osteoporosis (2D) Tertiary hyperparathyroidism Severe disease should be treated prior to TX (2D) Cinacalcet can be used in KTR (2C) Treatment same as for other CKD patients (2D) Gout
Neither allopurinol nor febuxostat used with azathioprine (1C)
Hyperuricaemia treated if associated with gout, tophi or uric acid stones (2D)
NSAIDs should be avoided (2D)
Acute gout treated with a course of oral prednisolone. (2D)
Colchicine is effective for gout (2D) CNI bone pain
Reduce or withdraw if intractable bone pain (2D)
Dihydropyridine CCBs may benefit (2D) …………………………………….. 10. Haematological Complications Anaemia Treated similar to other patients with CKD (2D) Polycythaemia
Treated with ACEIs or (ARBs) (1C)
Haemoglobin monitored at every visit (2D)
Treatment if PCV >52% in men & 49% in women (2D)
Venesection in refractory cases (2D) …………………………………….. 11. Reproduction Conception & contraception (female) MPA stopped before pregnancy (1A)
Wait for 1 year before attempting conception (2C)
Counselling regarding fertility offered before or soon after TX (2D)
m-TORi replaced prior to conception (2D)
Pregnancy jointly managed with an experienced Obstetrician (2D)
Aspirin 75 mg/day to reduce risk of pre-eclampsia from 12 weeks gestation until birth (2C)
Risks & benefits of breastfeeding discussed (2D) Conception & contraception (male)
MPA theoretically teratogenic (1D)
m-TORi reduce the male sperm count (1C)
Men who wish to maintain fertility should avoid m-TORi or bank sperm (2D) Sexual dysfunction
Care pathways for sexual dysfunction should be established (2D)
Close liaison with local andrology service is recommended (2D)
Sildenafil is safe & effective (if not taking nitrates) (2D) /////////////////////////// 2.What is the evidence provided by this article? Level V
ISAAC BUSAYO ABIOLA
2 years ago
SUMMARY
Introduction
This document was designed to provide guidelines to the management of care of post kidney transplant recipient outside of the primary hospital where the surgery was performed. It covers care on the early post operative stage where the rate of graft rejection is very high and also care of the later phase when recipient is prone to chronic rejection of malignancies. Moreso, the document provides different grading system and evidence of practice for any opinion from the expects
KTR clinic infrastructure
a dedicated outpatient area for review
a consultant level care
availability of blood tests results within 24 hours
review of result by health care staff within 24 hours
access to multidisciplinary renal team
KTR clinic frequency
2-3 times weekly for the first month
1-2 times weekly for next 2-3 months
2-4 weeks for the next 4-6 months
4-6 weeks for the next 6-12 months
3-6 monthly after
Recognition of non-adherence
factors associated with non -adherence should be identified
established pathway to identify and treat
special care to be paid to pediatrics patient
Induction immunosuppression
drugs should be started before or at the time of transplantation
the time of the induction drugs will depend on the level immunological risk in the recipient; low, medium, or high
CNI to be started at the time of transplantation
Maintenance immunosuppression
should consist of CNI inhibitors, steroid, and antiproliferative
the tacrolimus trough level will depend on the level of immunological risk
CNI is advice to always be part of the maintenance therapy
sirolimus trough level should be monitored
result of tacrolimus or sirolimus level should be ready within 24 hours of blood collection
azathioprine should replace MMF or myfortic for female recipient willing to get pregnant.
Diagnosis of acute rejection
allograft kidney biopsy be done for every case of acute rejection before starting treatment except otherwise
routine C4d and SV40 staining should be used
serum sample for DSA to be done
Treatment of acute rejection
high dose steroid should be started in those on steroid free regimen in any time of rejection
lymphocyte depleting can be considered for refractory cellular or aggressive vascular rejection
ABMR should be treated with any of the following steroid, plasmapheresis, IVIG, anti-CD20, lymphocyte depleting antibody or bortezomib
azathioprine should be switched to MMF or dose of MMF increase
Treatment of chronic allograft rejection
withdrawal of CNI if is due to it toxicity on histology
intensification of immunosuppressives if due ongoing immune injury either ABMR or cellular
For BKN, reducing of stopping immunosuppressives has been tried
Management of cardiovascular risk and disease
blood pressure check at every clinic and target BP <140/90mmHg, or <130/80mmHg if PCR >50mmol/l, or UPCR >30mmol/l
lipid should be checked x 2 yearly and use of statin not > 40mg daily is encouraged
PTDM should be managed with endocrinologist and watching out for micro and macrovascular complications
for ischemic heart disease thrombolysis, revascularization, and secondary prevention has a role
Life style measures
healthy diet
idea body weight with BMI of <25
participation in physical activities
reduce alcohol and avoid over the counter drug
avoid recreational drug
regular cancer screening as required especially skin
avoidance of life attenuated vaccine
Prophylaxis against the following
CMV
EBV
VCV
PJP
Conception and contraceptives
lady not to get pregnant until after a year with stable allograft function
stop antiproliferative in preparation for conception
men still willing to have baby should not be on mTOR inhibitors
The level of evidence is 1
Mohammed Abdallah
2 years ago
Summarise this article
Introduction
These are clinical practice guidelines of Post-Operative Care in the Kidney Transplant Recipient; January 2017 (reviewed February 2022)
Cover the initial period of transplantation from hospital discharge until graft failure or patient death
The management of KTR is divided into two phases:
1. an early post-operative period when the risks of acute rejection and infection are high (3-6 months)
2. a later phase when the aims are to preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression (> 3-6 months)
Outpatient Follow-up
Clinic infrastructure
A consultant should be available for every transplant clinic
Blood test results should be available within 24 hours
MDT including pharmacist, dietician, social worker and psychologist
Patient care should be planned
Clinic frequency
The first month (2-3 times weekly), 2-3 months (1-2 times weekly), 4-6 months (every 2-4 weeks), 6-12 months (every 4-6 weeks), and every 3-6 months after that
Patient access
All patients should have access to support services and results (on-line access, and open access to the renal transplant unit)
Information should be available in both written and electronic
Chronic transplant care review
Detailed review should be performed annually post-posttransplant and address concerns in medical, social, psychological and sexual domains
Renal dietician, social worker, specialist renal pharmacist and/or psychologist should be readily available
Non-adherence
Detect non-adherence with intervention for those at high risk of or with proven non- adherence
Immunosuppressive treatment
The patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression (1D)
Induction therapy should be administered to all KTRs and should be started before or at the time of renal transplantation. IL2-RA for low immunological risk and TDAs for high risk (TDAs may also be useful for lower immunological risk patients with steroid- or CNI-free regimen
Maintenance immunosuppression consist of a CNI and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs (1B)
Low-medium dose tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice in patients also taking steroids who are low-medium immunological risk and are not at high risk of developing PTDM
Mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception
Slow release tacrolimus may be used as an option as second line agents for patients who suffer intolerable side effects related to peak dose toxicity (2C)
KTRs who are unable to tolerate tacrolimus can use the second line agents such as ciclosporin, sirolimus, everolimus, or belatacept
MMF Myfortic provide equivalent maintenance immunosuppression (2B)
Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients (2B)
The minimum target levels for CNIs in uncomplicated renal transplantation after 3 months (2C)
CNIs should not be withdrawn (2B)
If steroids are not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less) (2C)
Long-term monitoring of immunosuppression levels is required
Drugs should be prescribed by brand name (whether branded or generic drugs are prescribed) (2D)
Acute rejection
Transplant renal biopsy should be carried out before treating an acute rejection episode unless this will delay treatment (16 gauge core biopsy needle and two cores of renal tissue)
Protocol transplant renal biopsyfor DGF (1C)
Do routine C4d and SV40 staining for biopsies to address other causes of graft dysfunction (2C)
Send serum sample at the time of renal biopsy for HLA-specific antibodies (2C)
Borderline acute cellular rejection should be treated in the context of acute graft dysfunction (2D)
High dose intravenous corticosteroids should be the first line treatment for acute cellular rejection (1D)
Maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type (2D)
Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III) (2C)
AMR should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib (2C)
After an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, or the existing dose of MPA maximised (2D)
Chronic Allograft Injury
Renal biopsy is the optimal investigation for parenchymal graft dysfunction where the cause is uncertain (2C)
Renal biopsies should be stained for C4d and SV40 (2C)
Serum sample should be sent for HLA- specific antibodies (2C)
Treatment by withdrawal of CNI if there is histological evidence of CNI toxicity and intensification of immunosuppression
Cardiovascular Disease and Lifestyle
Hypertension
BP should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
No evidence that any antihypertensive agent is better than any other
ACI/ARB is effective in proteinuria but should be used with caution in the first 3 months post-transplant. (2C)
Resistant hypertension may be due to transplant RAS
Dyslipidaemia
Do fasting lipid annual and the target is same as in the general population (2C)
Give statin risk of high risk of CAD (2C)
High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/ calcium channel antagonists (2D)
Diabetes mellitus
The diagnosis of PTDM is made based on WHO criteria
KTR with diabetes should undergo screening for diabetic complications (2D)
IHD
Receive standard treatment for IHD, including thrombolysis, revascularisation, and secondary prevention (2C)
Smoking cessation
Smoking should be strongly discouraged in transplant recipients (1A)
Lifestyle measures
Maintenance of a healthy diet, ideal BMI ((BMI) ≤25 kg/m2), participate in physical activity, and avoid alcohol consumption, recreational drug and the use of over-the-counter medications
Neoplasia
Screening is similar to the general population for cervical, breast, colon and prostate cancer (2C)
Educate patient about the adverse effects of sun exposure
Patients should be encouraged to cover their skin in direct sunlight and to use total sunblock (Sun Protection Factor ≥50) (1D)
Reduce immunosuppression if neoplasia develops
m-TORi are alternative immunosuppressive agents in KTRs who develop de novo malignancy (2C) and have specific anti-tumour effects in Kaposi sarcoma (2C)
Infection Complications
Vaccination with inactivated viruses as per the normal population (1D). Influenza vaccination annually, HBV if HBsAb < 10 mIU/mL and pneumococcal vaccine and a booster every five years
Prophylaxis of CMV for 3-6 months. Do serology and viral load. The first line treatment of life-threatening CMV disease is intravenous ganciclovir
For EBV infection, reduce the dose of immunosuppression. Do serology for both donors and recipients, and high risk should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year
Patients on the waiting list who are VZV IgG negative should be vaccinated prior to transplantation and. Reduce the dose of immunosuppression
Systemic HSV infections should be treated with intravenous aciclovir and a reduction in immunosuppression until a response occurs and oral medication should be continued for at least 14 days (1C)
For confirmed BK nephropathy reduce the dose of immunosuppression
Other infections are pneumocystis jirovecii infection and HEV
Bone and Joint Disease
Osteoporosis: steroid-free regimen for high risk patients and do DEXA scanning if eGFR >30. Treatment according to RCP guidelines for steroid-induced osteoporosis (2D)
Tertiary hyperparathyroidism: Treatment is the same as for other patients with CKD/cinacacet
Gout: not give allopurinol or febuxostat with azathioprine (1C). treat with predisolone/ colchicines and avoid NSAIDs
CNI bone pain: reduce the dose/dihydropyridine calcium antagonists
Haematological Complications
Anaemia: manage is the same as in CKD/ACEIs/ARBs
Polycythaemia: Venesection may be used in refractory cases
Reproductive Issues
Conception and contraception (female): wait for one year after transplant, counseling prior to transplantation, stop MMF/m-TORi prior to conception, and receive aspirin 75 mg daily from 12 weeks gestation
Conception and contraception (male): m-TORi reduce the male sperm count and counselled accordingly and/ theoretical teratogenicity for MPA containing compounds
Sexual dysfunction: Sildenafil is safe and effective in male KTR not taking nitrates (2D)
What is the evidence provided by this article?
Level 1 (Clinical practice guidelines)
Induction therapy should be given for all transplant recipients with preference of IL2-RAin low risk patient and ATG in high risk patients, except in case of steroid or CNI avoidance, low risk patients can be considered for ATG.
Induction therapy should be given before or at the time of transplantation
Maintenance immunosuppression
The recommended maintenance therapy should contain a calcineurin inhibitor (better tacrolimus), antimetabolite(better MMF) with or without steroids, and CNI should be started at the time of transplantation and should not be delayed after exclusion of DGF.
Using genericis not recommended except if it is proved that it is bioequivalent.
Mycophenolate mofetil (and enteric-coated mycophenolatehave the same efficacy, azathioprine may be preferred in females in child bearing age who are unwilling to use contraception
Steroidsare not associated with increase in the risk of PTDM, and if steroid avoidance or withdrawal is planned (in low risk patients) it is better to be in the first week after transplantation, and if not withdrawn in the first month it should be continued for life in low dose.
KTR: Monitoring of immunosuppression
Tacrolimus and ciclosporin levels should be monitored.
The initial frequency should be three times a week.
Levels should also be checked when any medication with possible interactions is prescribed.
Tacrolimus should be monitored by the trough (C0) level, while ciclosporin can be monitored by either C0 or 2- hour post dose (C2) level (2C)
Tacrolimus and ciclosporin levels should be available within 24 hours of taking blood samples in the first three months after transplantation.
The utility of monitoring mycophenolic acid (MPA) C0 levels is uncertain .
Sirolimus should be monitored by the C0 trough level .
Acute rejection
Before treating acute rejection, we advocate a transplant kidney biopsy unless it would delay therapy or put the patient in danger .
We propose considering a protocol transplant renal biopsy in the context of persistent delayed graft function .
For acute cellular rejection, we prescribe high-dose intravenous corticosteroids.
Refractory acute cellular rejection or aggressive vascular cellular rejection (Banff category 4 Type II and III) may benefit from lymphocyte-decreasing drugs .
AMR should be treated with steroids, plasma exchange, intravenous immunoglobulin, anti-CD20 antibody, lymphocyte-depleting antibody, or bortezomib .
After rejection, azathioprine should be transferred to MPA-based immunosuppression, MPA should be begun, or the current dosage of MPA should be increased.
Chronic Allograft Injury
At each clinic visit, renal function should be assessed by serum creatinine and urine protein excretion by dipstick, augmented by spot protein: creatinine ratio (PCR) or albumin: creatinine ratio (ACR) if positive .
Chronic allograft injury should be treated with:
Withdraw calcineurin inhibitors if histology shows CNI toxicity or non-specific interstitial fibrosis and tubular atrophy .
By intensifying immunosuppression, if immunological damage (cellular or humoral) persists .
KTR:Hypertension
Monitoring of hypertension after kidney transplantation can be done using clinic, hoe and ambulatory BP monitoring with target clinic BP < 140/90, home and day time ABPM < 135/80 with lower target can be set for patients with proteinuria (< 130/80).
Any antihypertensive medication can be used , ACE or ARBS may be preferred in case of proteinuria but caution should be don in the first 3 month after transplantation.
With resistant hypertension should be screened for RAS.
KTR: Dyslipidaemia
Fasting lipid levels should be measured on an annual basis in renal transplant recipients .
KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease.
The choice and dose of statin should take into account concurrent immunosuppression.
High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/calcium channel antagonists.
KTR: Diabetes mellitus
Screening for the development of post-transplant diabetes mellitus (PTDM) by dipstick urinalysis and measurement of blood sugar level at each clinic visit .
Post-transplant immunosuppression should take into account risk factors for the development of diabetes .
The diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing .
A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression .
Post-transplant diabetes should be managed in collaboration with specialists in diabetic medicine .
KTR: Ischaemic heart disease
Standard treatment for ischaemic heart disease, including thrombolysis revascularisation, and secondary prevention .
KTR: Smoking cessation
Smoking should be strongly discouraged in transplant recipients .
KTR: Lifestyle measures
Stop smoking, maintain ideal body weight (BMI ≤25 kg/m2), adopt healthy life style including healthy diet and regular exercise at least 150 minute per week.
Not intake any medications should be avoided without discussion with clinical staff.
KTR: Screening for cancer
Screening should be similar to the general population for cervical, breast, colon and prostate cancer.
Screening is not recommended for renal cell carcinoma .
Patient education pre and post transplantation .
Patients should be aware of malignancy risk and encouraged to report symptoms which may represent de novo malignancy (e.g. breast or testicular lumps) .
Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant .
Patients with cirrhosis should undergo an annual hepatic ultrasound and determination of serum alpha fetoprotein .
KTR: Vaccination
Renal transplant recipients should receive inactivated as general population and should not receive live attenuated vaccines.
Recipients should receive influenza vaccine annually unless contraindicated
Pneumococcal vaccine should be received every 5 years
HBsAb levels should be checked annually and the patient should be revaccinated if the titer < 10 mIU/mL.
KTR: Prophylaxis and treatment of CMV disease
Serological status of the donor and recipient should be known
KTR should receive prophylaxisfor 3- 6 months till reduction of immunosuppression according to the serological status of the donor and recipient
Treatment should be received for 6 weeks after giving ATG
For mild and moderate CMV disease, oral valgancycloverand IV gancyclover are equal in efficacy while IV gancyclovir is the treatment of choice in case of severe life threatening CMV infection
The duration of treatment should be based on the viral load.
KTR: EBV infection
Both donor and recipient should have their EBV serology recorded at the time of transplantation.
All high risk (D+/R-) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year .
EBV viral load should be monitored after the treatment of rejection.
KTR: Varicella Zoster Virus (VZV) infection
VZV should be treated with oral valacyclovir(uncomplicated) or IV acyclovir (disseminated> 2 dermatomes) until lesions scab over.
And reduction of immunosuppression should be considered only in disseminated infection KTR who test negative for VZV IgGshould be vaccinated before transplantation.
and if they are exposed to HZV (without vaccination) they should receive IVIG within 4 days of exposure (maximum 10 days) together with 67 day course of oral acyclovir.
Immunosuppression should be reduced during infection.
KTR: Herpes Simplex Virus (HSV) infection
Superficial HSV infection should be treated with appropriate oral agents until the lesions have resolved.
Systemic HSV infections should be treated with intravenous aciclovir and a reduction in immunosuppression until a response occurs and oral medication should be continued for at least 14 days .
KTRs suffering frequent recurrent HSV infection should consider oral prophylaxis.
KTR: BK virus (BKV) nephropathy
Screening should also be carried out when renal function deteriorates in an unexplained fashion .
KTRs should be screened for BKV viral load or by performing urine microscopy for decoy cells or by polymerase chain reaction (PCR) on urine or serum.
Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40.
Two cores containing medullary tissue should ideally be examined .
Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml .
There is no established specific treatment for BK nephropathy.
Re-transplantation can safely considered in patients who have BK nephropathy diagnosed in an earlier graft.
KTR: Pneumocystis jirovecii infection – treatment and prophylaxis
Pneumocytis Jirovecii infection; confirmed disease should be treated with oral or iv co-tirmoxazole for 2 to 3 weeks.
CTX 480 for 3-6 months is use for prophylaxis.
KTR: Osteoporosis
KTRs suffering from osteoporosis or at high potential risk should be considered for steroid-avoiding immunosuppression.
KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2 .
Treatment should be according to the Royal College of Physicians (RCP) guidelines for steroid-induced osteoporosis .
KTR: Tertiary hyperparathyroidism
Severe hyperparathyroidism should be treated prior to transplantation.
Cinacalcet can be used in KTR.
Treatment should be the same as for other patients with CKD .
KTR: Treatment of gout
Hyperuricaemia should be treated when associated with gout, tophi or uric acid stones .
Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided in KTRs.
Acute gout may be treated with brief a course of oral prednisolone.
Colchicine is an effective treatment for gout in KTR .
KTR: Calcineurin inhibitor bone pain
Reduction or withdrawal of CNIs should be considered in KTRs with intractable bone pain .
Dihydropyridine calcium antagonists also may be beneficial .
KTR: Anaemia
Should be treated as anaemia of CKD.
KTR: Polycythaemia
Should be with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) .
KTR: Polycythaemia
Haemoglobin levels should be monitored at every clinic visit .
Treatment should be initiated if the haematocrit or packed cell volume exceeds 52% in men and 49% in women.
Venesection may be used in refractory cases.
KTR: Conception and contraception (female)
MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately .
KTRs should wait for one year after transplant and have stable function before attempting conception.
Counselling regarding fertility and reproduction should be offered to female KTRs and their partners either prior to transplantation or soon afterwards.
m-TORi should be stopped prior to conception and replaced as appropriate .
Pregnancy should be jointly managed with an Obstetrics department with experience of care of KTR .
KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth of the baby unless there are contraindications .
The risks and benefits of breast feeding should be discussed .
Contraception advice should be similar to the general population.
KTR: Conception and contraception (male)
KTRs should be advised that m-TORi reduce the male sperm count and counselled accordingly.
All immunosuppressive drugs other than m-TORi can be used in male KTRs. Advice for MPA .
The decision to continue MPA containing compounds in a male KTR wishing to conceive should balance the risk of theoretical teratogenicity against the risk of rejection on changing from MPA to azathioprine .
Men on m-TORi who wish to conceive should discontinue these agents prior to conception and replace them as appropriate .
Men who wish to maintain fertility should avoid m-TORi or bank sperm prior to starting these drugs .
KTR: Sexual dysfunction
Specific enquiry should be made regarding sexual dysfunction, preferably at an annual review clinic .
Care pathways for dealing with sexual dysfunction should be established .
Close liaison with local andrology service is recommended .
Sildenafil is safe and effective in male KTR not taking nitrates.
Thank you very much Prof.Sharma
Yes, prof.
The level evidence is 5
Ban Mezher
2 years ago
Each kidney transplant center should include consultant level health professional , renal pharmacist, dietician, social worker & psychological personnel.
All KTR should be reviewed by specialist in out patient clinic with lab result available within 24 hr.
All KTR reviewed 2-3times/week in first month, 1-2times/week for 2-3 months, every 2-4 weeks for 4-6 months, every 4-6 weeks for 6-12 months, then every 3-6 months.
All patient or carer suggested to involved in chosen induction therapy & maintained immunosuppression
All recipient should receive induction therapy according to their immunological risk.
All recipients receive tacrolimus ( unless contraindicated)m MMF ( unless recipient didn’t want use contraception) with or without steroid as maintenance immunosuppression .
Tacrolimus drug level monitored by C0, cyclosporin by C0 or C2 & sirolimus by C0.
Immunosuppression should prescribed by brand name & monitor drug level closely when switched to another generic preparation.
Graft biopsy indicated if rejection suspected, routine stain with C4d & SV40.
ACR treated with pulse steroid & ATG for aggressive rejection.
AMR treated with steroid, PE, IVIG, rituximab , ATG or bortezumib.
Blood pressure should be checked in every visit with target <14/90 or <130/80 if proteinuria present.
TRAT suspected in sever resistant HT.
Lipid profile checked annually with treatment target similar t general population, but drug interaction with immunosuppression should be considered.
PTDM diagnosed according WHO criteria of DM diagnosis, with screening for diabetic complication. Specialist in diabetic medicine should be involved in treatment.
Encourage healthy life style & smoking cessation.
IHD treated by standard treatment.
Skin surveillance should be done annually with avoiding direct sun exposure in addition to encouraging self skin examination.
Switch to mTOR-I when neoplasm diagnosed.
Activated vaccination contra-indicated but inactive vaccines recommended as normal population.
CMV, P. jervicii prophylaxis for 3-6 months recommended for all KTR with oral anti fungal in first week post transplantation.
TB prophylaxis with INH for 6 months used for some recipients.
Patients with history of osteoporosis should undergo steroid free regime. Chronic anemia & hyperparathyroidism treated as CKD patients.
Parathyroidectomy should be done before transplantation if indicated.
Infection with BKV & EBV need reduction in immunosuppression.
Renal transplant health care facility should be consultant based with availability of MDT; investigation results including CNI level should be available within 24 hours and should be reviewed by health care professionals within also 24 hours of clinic visit in a dedicated outpatient clinic
Easy access to services is recommended that should include online access to the result of investigations
Non adherence should be evaluated by the health care professionals, with identification of risk factors and all efforts should be done to prevent this major problem
Renal transplant recipient and/or caregiver should be involved in the decision making regarding immunosuppression medication selection
Induction immunosuppression
Induction therapy should be given for all transplant recipients with preference of IL2-RA in low risk patient and ATG in high risk patients, except in case of steroid or CNI avoidance, low risk patients can be considered for ATG
Induction therapy should be given before or at the time of transplantation
Maintenance immunosuppression
The recommended maintenance therapy should contain CNI (better tacrolimus), antimetabolite (better MMF) with or without steroids, and CNI should be started at the time of transplantation and should not be delayed after exclusion of DGF
Using generic is not recommended except if it is proved that it is bioequivalent
MMF and enteric-coated mycophenolate have the same efficacy; azathioprine may be preferred in females in child bearing age who are unwilling to use contraception
Steroids are not associated with increase in the risk of PTDM, and if steroid avoidance or withdrawal is planned (in low risk patients) it is better to be in the first week after transplantation, and if not withdrawn in the first month it should be continued for life in low dose
Monitoring
In uncomplicated renal transplant recipient, the patient should be followed 2-3 times weekly in the first month, 1-2 times weekly in 2nd and 3rd month, 1-2 times per month till 6th month, monthly till first year and then every 3-6 months
The minimum investigations required for monitoring of KTR are creatinine, urine analysis, ACR, CNI level, blood glucose assessment and hemoglobin level
CNI level should be checked regularly as prescribed above using C0 (tacrolimus) or C2 OR 2(in cyclosporine) and the level should be rechecked if there is graft dysfunction, suspected drug-drug interaction, suspected non-adherence , change in the dose, or switching between generic and brand
Tacrolimus level should be maintained at 4-8 ng/ml using lower target in low risk patients, sustained released formulation can be considered as a second option in case of intolerable side effects related to the peak, and if not tolerated switching to cyclosporine or using CNI minimization or avoidance is advised
Sirolimus level should be monitored using C0, and monitoring of MMF is not recommended
In case of graft dysfunction (acute or chronic), the minimum investigations required includes
Renal biopsy using 16 gauge automated needle to obtain 2 cores with staining of C4d and SV40
Monitoring of CNI level and DSA
Renal biopsy is indicated in the following settings
Graft dysfunction with rising creatinine
Failure of return of creatinine after BPAR episode
New onset proteinuria (PCR >50 mg/mmol or ACR >35 mg/mmol)
In case of persistent DGF it is recommended to do a biopsy every 7-10 days till improvement
Diagnosis (using renal biopsy) should be confirmed before starting treatment except if there is suspicion of rejection and there is expected harm with treatment delay
Treatment of AR
In case of acute TCMR, the first line therapy is high dose steroids, ATG should be given if there is poor response to steroids or if there is associated aggressive vascular rejection. Border line TCR should not be treated except if there is graft dysfunction
In case of ABMR treatment should include on eor more f the following : IVIG, PE, Rituximab, ATG or bortezomib
After rejection it is recommended adjust the dose of CNI, maximize the dose of MMF or switch to MMF if was on azathioprine and start maintenance long term steroids if the patient was on steroid free protocol.
Chronic allograft dysfunction
The most common causes of chronic allograft dysfunction includes chronic CNI toxicity and IFTA which can be treated by minimization or avoidance of CNI or rejection which can be treated by intensification of immunosuppression
Hypertension after kidney transplantation
Monitoring of hypertension after kidney transplantation can be done using clinic, hoe and ambulatory BP monitoring with target clinic BP < 140/90, home and day time ABPM < 135/80 with lower target can be set for patients with proteinuria (< 130/80)
Any antihypertensive medication can be used , ACE or ARBS may be preferred in case of proteinuria but caution should be don in the first 3 months after transplantation
Any patient with resistant hypertension should be screened for RAS
Hyperlipidemia after kidney transplantation
Hyperlipidemia should be screened annually and managed as per general population, with respect to drug-drug interaction in which the use of simvastatin in a dose ≥40mg daily should be avoided when using ciclosporine and/or CCB
DM after kidney transplantation
Patients with diabetes should be screened for retinopathy, diabetic foot and neuropathy before transplantation
PTDM should not be diagnosed except after attaining stable level of immunosuppression , diagnosis can be done using FBG, PPBG, HBA1c or OGTT, and the treatment should be planned in collaboration with diabetic specialist
IHD after renal transplantation
Patient with IHD can be treated as non-transplant patients including thrombolysis, revascularization, and should offer secondary prevention
Life style after renal transplantation
Patient should stop smoking, maintain ideal body weight (BMI ≤25 kg/m2), adopt healthy life style including healthy diet and regular exercise and non-supervised intake of over the counter medications should be avoided
Malignancy after renal transplantation
Patient should know the risk of developing malignancy after transplantation
General screening as general population is recommended for cervical, breast, colon and prostate cancer
No screening for RCC
Self-examination of the skin is advised and skin surveillance by a specialist is recommended /6 months till 5 years after transplantation then annually
In patients with liver cirrhosis AFP and US should be done annually
The patient should be informed about the danger of direct sun exposure, and should be educated either to cover the skin of to use sun block (Sun Protection Factor ≥50)
Treatment of cancer after transplantation should include reduction of the immunosuppression with shifting to m-TORi in case of denovo malignancy especially kaposi sarcoma, other therapies will differ according to the stage and type of malignancy, for example acitretin is indicated if there are ≥2 NMSC provided there are no contraindications
Vaccination
Renal transplant recipients should receive inactivated vaccines as general population and should not receive live attenuated vaccines
Recipients should receive influenza vaccine annually unless contraindicated
Pneumococcal vaccine should be received every 5 years
HBsAb levels should be checked annually and the patient should be revaccinated if the titer < 10 mIU/mL
CMV prophylaxis and treatment
Serological status of the donor and recipient should be known
KTR should receive prophylaxis for 3- 6 months till reduction of immunosuppression according to the serological status of the donor and recipient
Treatment should be received for 6 weeks after giving ATG
For mild and moderate CMV disease, oral valgancyclover and IV gancyclover are equal in efficacy while IV gancyclovir is the treatment of choice in case of severe life threatening CMV infection
The duration of treatment should be based on the viral load
EBV prophylaxis and treatment of PTLD
Serological status of the donor and recipient should be known
In high risk patients (D+/R-) it is recommended to measure viral load immediately after transplantation, monthly for 6 months, and every 3 months till the first year post transplantation and after treatment of rejection
Reduction of immunosuppression is indicated if EBV titer increased significantly
Immunosuppression should be reduced or stopped if the patient develop PTLD
VZV infection
VZV should be treated with oral valacyclovir (uncomplicated) or IV acyclovir (disseminated> 2 dermatomes) until lesions scab, and reduction of immunosuppression should be considered only in disseminated infection
KTR who test negative for VZV IgG should be vaccinated before transplantation and if they are exposed to HZV (without vaccination) they should receive IVIG within 4 days of exposure (maximum 10 days) together with 67 day course of oral acyclovir
Immunosuppression should be reduced during infection
HSV infection
Superficial HSV infection should be treated with oral acyclovir till lesions resolved
Systemic HSV infection is retreated by transient reduction of immunosuppression till resolution, IV acyclovir till improvement then switching to oral acyclovir for 2 additional weeks
Patient with recurrent HSV infection should be considered for prophylaxis
BK nephropathy
KTRS should be screened for BK virus using urine for decoy cells, urine or blood PCR if there is graft dysfunction and biopsy should include2 cores containing medulla with staining for SV40
The main treatment of BK nephropathy is reduction of immunosuppression if the serum BKV load >104 copies/ml since there is no specific antiviral therapy
Pneumocystis jirovecii infection prophylaxis and treatment
All patients should receive prophylaxis for Pneumocystis jirovecii for 3-6 months after transplantation
Co-trimoxazole is the drug of choice given in a dose of 480 mg daily
Patients with Pneumocystis jirovecii infection should be treated for 2-3 weeks with co-trimoxazole orally or intravenously (15-20mg/kg in 3-4 divided doses) and if contraindicated IV pentamidine (4mg/kg/day) is an alternative
In severe cases steroids can be used
Prophylaxis against other infections
Oral antifungal prophylaxis shpuld be give in the firsyt week after transplantation
Daily INH is recommended for 6 months after transplantation in case of latent TB
Bone problems with transplantation
Patients at high risk of osteoporosis should be considered for DEXA scan (if GFR> 30) and for steroid free regimen
Treatment of osteoporosis is according to guidelines of steroid induced osteoporosis
Severe hyperparathyroidism should be treated before transplantation as with CKD patients, cinacalcit can be used
In patients with intractable bony pain (CNI induced bone pain), reduction or withdrawal of CNI should be tried, and adding CCB may be of value
Treatment of hyperurecimia / gout
Hyperuricemia is treated only if symptomatic (gout, tophi or uric acid stones)
The use of allopurinol or febuxostat is not recommended in combination with azathioprine
NSAIDS should be avoided
Acute gouty attack can be treated either with brief course of corticosteroids or colchicine
Haematological Complications
Anaemia should be treated as anaemia of CKD
Polycytyhemia should be treated when PCV > 52% in male and > 49% in female, initial treatment using ACE/ARBS and if not responding venesection may be used
Conception and contraception (female)
MPA and m-TORi should be stopped before conception and replaced appropriately
Contraception plan should be clear and should be offered before transplantation
Breast feeding should be discussed with the patient according to medications given
The ideal time for conception is after 1 year post transplantation provided there is stable graft function with no history of AR in the past 6 months
Asprin 75 mg should be given to all pregnant KTR after 12 weeks of gestation till birth
Pregnancy should be managed by obstetrics department experienced in kidney transplantation
Conception and contraception (male)
The patient should know that MPA is teratogenic and the use of m-TORi may reduce the sperm count
Male who want to conceive should stop MPA, while who want to maintain fertility should not take m-TORi or take it after sperm banking
Sildenafil is safe and can be used in renal transplant recipients not taking nitrates
I liked reading your summary and analysis. This is level 5 evidence, not level 1. Ajay
Weam Elnazer
2 years ago
Summary of Clinical Practice Guidelines for the Post-Operative Care of the Kidney Transplant Recipient:
Clinic building:
KTR follow-up (2D) requires the following infrastructure:
Every transplant clinic should have a consultant-level healthcare professional.
KTRs should be reviewed in a dedicated outpatient area Blood test results (including drug levels, if possible) should be available within 24 hours.
A formal mechanism should exist for results review by healthcare professionals within 24 hours of a clinical appointment.
A multidisciplinary renal team, comprising a pharmacist, nutritionist, social worker, and psychologist, should be available.
Patient treatment should be organized according to the National Service Framework and “Kidney Health Delivering Excellence.
Immunosuppression:
-Immunosuppressants should be started before or during kidney transplantation (1B)
-All KTRs need biological induction treatment. In low-risk patients, an interleukin-2 receptor antagonist is used (IL2-RA). T-cell-depleting antibodies (TDAs) may be given to high-risk patients (1B)
-Lower immunological risk individuals who want to avoid steroids or calcineurin inhibitors (CNIs) may benefit from TDA induction treatment (1C)
-We propose starting a CNI upon transplantation, not after the graft is functional (2C)
-In moderate and medium immunological risk KTRs, we prescribe a calcineurin inhibitor (CNI) and an anti-proliferative drug, with or without corticosteroids (1B)
-Low-medium dosage tacrolimus (trough goal 4-8 ng/mL) is indicated as the CNI of choice in patients already taking steroids who have low and medium immunological risk and are not at high risk of developing PTDM (2C)
-Mycophenolic acid-based medicines should be the first-line anti-proliferative treatment above azathioprine, except in fertile KTRs reluctant to take contraception (2B)
Acute rejection:
–Before treating acute rejection, we advocate a transplant kidney biopsy unless it would delay therapy or put the patient in danger (1C)
-We propose considering a protocol transplant renal biopsy in the context of persistent delayed graft function (1C)
-For acute cellular rejection, we prescribe high-dose intravenous corticosteroids (1D)
-Refractory acute cellular rejection or aggressive vascular cellular rejection (Banff category 4 Type II and III) may benefit from lymphocyte-decreasing drugs (2C)
-AMR should be treated with steroids, plasma exchange, intravenous immunoglobulin, anti-CD20 antibody, lymphocyte-depleting antibody, or bortezomib (2C)
-After rejection, azathioprine should be transferred to MPA-based immunosuppression, MPA should be begun, or the current dosage of MPA should be increased (2D)
Chronic Allograft Injury:
–At each clinic visit, renal function should be assessed by serum creatinine and urine protein excretion by dipstick, augmented by spot protein: creatinine ratio (PCR) or albumin: creatinine ratio (ACR) if positive (2C)
-Chronic allograft injury should be treated with:
Withdraw calcineurin inhibitors if histology shows CNI toxicity or non-specific interstitial fibrosis and tubular atrophy (2C)
By intensifying immunosuppression, if immunological damage (cellular or humoral) persists (2C)
Hypertension:
-Clinic blood pressure should be <140/90 mmHg in the clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
Dyslipidaemia-
– Treatment targets should be the same as in the general population (2C)
Diabetes mellitus:
-PTDM is diagnosed based on fasting or random blood, serum glycated hemoglobin (HBA1c), or oral glucose tolerance tests (1C)
Smoking cessation
We recommend that smoking should be strongly discouraged in transplant recipients.
Screening for cancer –Screening should be similar to the general population for cervical, breast, colon, and prostate cancer (2C)
-Skin monitoring biannually up to 5 years post-transplant and yearly after 5 years (2C)
-We suggest that immunosuppression should be reduced if neoplasia develops (2C)
-We suggest that mammalian targets of rapamycin inhibitors (m-TORi) are considered alternative immunosuppressive agents in KTRs that develop de novo malignancy (2C)
CMV therapy and prevention
-Prophylaxis should be maintained for 3-6 months until immunosuppression is at a maintenance level (1B)
EBV
-We advocate reducing or stopping immunosuppression after PTLD (1C)
BK nephropathy
-We recommend that confirmed BK nephropathy should be treated by a reduction in immunosuppression (1D)
Conception and contraception (female)
– We recommend that MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately (1A)
I liked reading your summary and analysis. This is level 5 evidence, not level 1. Ajay
Nandita Sugumar
2 years ago
Summary
This article is about the post op care of kidney transplant patients, which includes identifying and diagnosing accurately symptoms of rejection and other issues that can affect graft and patient outcome, along with its appropriate treatment. Long term outcome is important and this is kept in mind while monitoring patient in the post operative phase. Since immunosuppression regimen plays a crucial role in the success or failure of the transplant and patient survival rates, it has special details that need to be followed.
The clinical practice guidelines include the following :
A consultant available in every transplant clinic, with a dedicated OP area.MDT is also needed – physician, psychologist, pharmacist, dietician, social worker.
Blood test results need to be available within a day along with review.
Patient review for uncomplicated cases reduces in frequency with time, starting from twice a week the first month post transplant later reducing to once in 6 months.
Annual review to be conducted regularly.
Assessment to identify non-adherence to medication along with pathways for pediatric and adolescent KTRs.
Induction therapy includes a CNI at the time of transplant. Maintenance includes CNI, anti proliferative agents, steroids.
MMF based drugs can be used except for patients who want to get pregnant.
Steroid avoidance can be used during the first week post transplant in low risk KTRs.
Kidney biopsy is done to diagnose acute rejection.
Renal function is checked at every clinic visit – serum reatinine, urine protein excretion by dipstick, spot protein : creatinine ratio (PCR) or albumin : creatinine ratio (ACR) if positive
Renal biopsy when cause of graft dysfunction is unknown followed by C4d staining, look for HLA specific antibodies. Renal biopsy is also indicate when there is persistent unexplained elevation of serum creatinine or failure to return to baseline following rejection episode, in the case of DGF, expected renal function not achieved within 8 weeks, new onset proteinuria which is sustained.
Withdrawal of CNI is to be down if there is evidence of toxicity such as interstitial fibrosis or tubular atrophy.
Intensify immunosuppression if there is ongoing immune injury in the form of cellular rejection or humoral rejection
BP measurement to be done at each visit followed by investigation for renal artery stenosis if patient has resistant hypertension despite medications.
Inhibitors of RAAS can be used in hypertensive patients with proteinuria for better outcome., However, this is to be used after 3 months post transplant.
Lipid levels are to be measured annually since patient is at risk of primary or secondary cardiovascular disease. Statins are to be advised to the patient to reduce risk of coronary heart disease.
Diabetes assessment post transplant for PTTDM – dipstick urinanalysis along with blood sugar level measurement at each clinic visit.
Counseling for smoking abstinence to appropriate patients.
Encouragement for healthy lifestyle measures such as losing weight, health diet, moderate intensity regular exercise along with avoidance of over the counter medication without discussing with the clinical staff, moderate or low alcohol consumption, and avoidance of recreational drugs.
Cancer screening for cervical, breast, colon, and prostate cancer. Skin surveillance twice a year for the first five years post transplant and every year after that.
Annual hepatic ultrasound for cirrhosis patients along with serum alpha feet protein measurement.
Measurement and assessment of infection and viral load is to be done.
Gout patients should not be given allopurinol or febuxostat with azathioprine. Colchicine is effective treatment and should be used along with short course of oral prednisolone. Avoid NSAIDs in these patients.
Level of evidence
This is clinical practice guidelines, hence level of evidence is 1.
Clinic visits; 2-3 /week the first month,1-2 times weekly for 2-3 months, every 2-4 weeks for 4-6 months, every4-6 weeks for 6-12 months, and 3 -6 months thereafter
Recognizing non-adherence; factors associated with it must be identified,pediatrics requires special pathway
Immune-suppression; induction by IL2A for low risk and lypmhodepleting agents for high risk. Maintenance should include CNIs+ anti-proliferative agents with without steroid in low and medium immunologic risk
Diagnosis of acute rejection; biopsy is mandatory
Treatment of acute rejection; high dose steroid, lypmhodepleting agents or refractory of Banff II & III
Diagnosis of CAN; requires biopsy and treatment may include withdrawal CNIs in cases of toxicity or intensification of immune-suppression in cases of immunologic injuries
Optimization of the cardiovascular risk and life styles; control of BP, lipids and screening for PTDM plus smoking cessation.
Cancer screening; biannually up 5 years post Tx and annually after the 5 years
Vaccination; Avoid live attenuated vaccine, should receive the other forms of vaccine
CVM disease; prophylaxis for 3-6 months and treatment is for 6 week after TDA
EBV infection; reduce or stop immune suppression after the diagnosis of PTLD
VZV infection; Vaccinate those who are IgG -ve , treat primary infection by IV or oral acyclovir or valacyclovir untill the lesions scab over, reduce immune-suppression
BK nephropathy; reduce immune suppression, and screen those with allogarft dysfunction
Pneumocytis Jirovecii infection; confirmed disease should be treated with oral or iv co-tirmoxazole for 2 to 3 weeks. CTX 480 for 3-6 months is use for prophylaxis.
Osteoporosis; avoid steroids, screen those on steroids with DEXA scanning if eGFR>30 and treat according to RCP guidelines
Tertiary hyperparathyroidism; treat severe secondary hyperparathyroidism before transplantation
Gout; avoid use of allopurinol or febuxotat with azathioprine, avoid NSIADs
Anemia management; same as CKD
Polycythemia; treat with ACE-I/ARBS if haematocrit > 52% in men and >49% in women. Consider venesection in refractory cases
Conception and contraception(Female); discontinue MMF/MPA before conception and replaced appropriately( the same applies to mTORi). Pregnancy is allowed after one year with a stable graft function. Counseling and education must be done for the couples before transplantation. The management should be with obs&gyne team experienced with transplantation.
Conception and Contraception(Male); MPA/MMF and mTORi may not be a good option. Those who are willing to conceive may be advise to bank sperm before beginning these drugs.
Sexual dysfunction; patients musk be ask about this during the visit and problems can be address through collaboration with local andrology. Sildenafil may be considered in those who are not taking nitrates.
The management of KTR can be divided into two phases:
An early post-operative phase when prevention of acute rejection, optimization of graft function and prevention of opportunistic infection are paramount
b. a later phase when the aims are to preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression – malignancy, infection and premature cardiovascular disease.
Transplantation place, staff should be available, frequency set as standard protocol, most
Frequent in the first month ,reduced gradually to 1-2 times in next month then weekly in coming third month ,then monthly up to one year , then every 3months or more depend on patient condition.
Patient access:
Should have an open access to transplant team, on line access and patient information written and instruction given Cleary?
Patient should have an integrated annual examination with multi-disciplinary team
Immunosuppression regimen:
Induction therapy:
With biological agents should be administered to all KTRs.
In an interleukin-2 receptor antagonist in low immunological risk.
T-cell (lymphocyte) depleting antibodies in higher immunological risk. TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor avoidance.
CNI should be started at the time of transplantation and not delayed until the graft is functioning.
Maintenance immunosuppression:
Calcineurin inhibitor (and an anti-proliferative agent (MMF), with or without corticosteroids in low and medium immunological risk KTRs.
Minimum target levels for CNIs in uncomplicated renal transplantation after 3 months
Not tolerant KTR to tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second line agents such as cyclosporine, sirolimus, everolimus, or belatacep.
Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients. If not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less).
Monitoring of immunosuppression:
Should be done initially 3 times per week, using trough (TAC and Sirolimus) OR Co or C2 for CSA.
Acute rejection:
Biopsy should be done, protocol biopsy in case of persistent DGF.
C4d and SV40 staining should be performed.
HLA specific antibodies.
Treatment of acute rejection:
Borderline acute cellular rejection should be treated in the context of acute graft dysfunction.
High dose intravenous corticosteroids should be the first line treatment for acute cellular rejection.
Maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type.
Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III).
AMR: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib.
After AR – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximized.
Chronic Allograft Injury:
By biopsy, C4d and SV 40 should be done.
HLA antibodies.
Treatment of chronic allograft injury
Treat any underlying cause (ABR or CMR, CNI toxicity), Preventive measures for CKD.
Renal biopsy in chronic allograft injury:
We suggest that a renal transplant biopsy is indicated:
· If there is a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection (BPAR) (1C)
· Every 7-10 days during delayed graft function (DGF) (2C)
· If expected renal function is not achieved within 4-8 weeks (2D)
· If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol) (2C)
Hypertension:
Regular check, keep below 140/90, no specific antihypertension, caution with ACI in first 3months.
Dyslipidemia:
As in general population should be controlled, avoid high dose simvastatin with CNI and CCB.
Diabetes mellitus:
Screen regularly, use WHO criteria to diagnose it, follow for complication.
Ischemic heart disease:
KTRs receive standard treatment for IHD, including thrombolysis, revascularization, and secondary prevention.
Lifestyle measures
We suggest that advice on healthy lifestyle, DIET, WEIGHT, BMI less 25 kg/m2, exercise .avoid smoking and non-prescribed medication.
Screening for cancer:
· Screening should be similar to the general population for cervical, breast, colon and prostate cancer
· Screening is not recommended for renal cell carcinoma.
Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant.
To cover their skin in direct sunlight and to use total sunblock, (Sun Protection Factor ≥50).
Vaccination:
We recommend that KTRs:
· Should be vaccinated with inactivated viruses as per the normal population (1D)
· Should receive annual influenza vaccination unless contraindicated.
Should have hepatitis B surface antibody (HBsAb) levels rechecked annually and be revaccinated if antibody titres fall below 10 mIU/mL (2D)
· Should not receive live attenuated vaccines (2C)
· Should receive pneumococcal vaccine and a booster every five years.
Cytomegalovirus (CMV) disease Guideline:
· Prophylaxis should be continued for 3-6 months, until immunosuppression has been reduced to long-term maintenance level (1B)
· Treatment should be administered for 6 weeks after treatment with a TDA.
EBV infection:
Recommend that immunosuppression should be reduced or stopped following the development of post-transplant lymphoproliferative disease.
All high risk (D+ /R- ) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year (2C)
· EBV viral load should be monitored after the treatment of rejection (2C)
· Total immunosuppression should be reduced when EBV tires rise significant.
Varicella-susceptible KTRs (i.e. VZV IgG negative) with primary exposure to VZV should receive intravenous immunoglobulin, ideally within 96 hours, but up to a maximum of 10 days following exposure. If unavailable or after 10 days, oral acyclovir should be prescribed for seven days.
VZV infection:
· Primary infection (chickenpox) should be treated with intravenous acyclovir or oral valaciclovir until the lesions scab over (1C)
· Uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over (1D)
· Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with intravenous acyclovir until the lesions scab over, together with a reduction in immunosuppression.
BK nephropathy:
We recommend that confirmed BK nephropathy should be treated by reduction in immunosuppression.
Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml.
Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40.
Pneumocystis jirovecii infection:
-All patients with confirmation (microscopy or PCR) of Pneumocystis jirovecii in respiratory secretions should be treated for 14 to 21 days with co-trimoxazole orally or intravenously (15-20mg/kg in three or four divided.
Contraindications to treatment with co-trimoxazole should receive pentamidine (4mg/kg/day intravenously) (2B)
· Adjunctive glucocorticoid in severe disease (2D)
· All patients should receive 3-6 months of treatment with co-trimoxazole 480mg daily for prophylaxis following renal transplantation.
Osteoporosis:
DEXA scanning if eGFR >30.
Tertiary hyperparathyroidism:
· Severe hyperparathyroidism should be treated prior to transplantation.
Cinacalcet can be used.
Treatment of gout:
If stone, gout and tophi,
Neither allopurinol nor febuxostat should be administered with azathioprine.
Acute gout may be treated with brief a course of oral prednisolone. (2D)
· Colchicine is an effective treatment for gout in KTR.
Anemia:
We suggest that chronic anemia should be managed in the same way as other patients with CKD. Polycythemia: initial treatment should be with ACEIs or ARBs.
Venesection may be used in refractory cases.
Conception and contraception (female):
Stop MMF and mTor prior to pregnancy, delay pregnancy for one year.
KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth of the baby unless there are contraindications.
All immunosuppressive drugs other than m-TORi can be used in male KTRs.
Sexual dysfunction
Close liaison with local andrology service is recommended.
· Sildenafil is safe and effective in male KTR not taking nitrates.
Level of evidence V.
BTS guidelines:
For management of patients post kidney transplant from all sides:
1-infrastructure of hospital and clinic
2-Counselling of patients
3-induction and maintenance immunosuppression
4-infections
rejection treatment
contraception
level 5 evidence
This is a guideline for post-up care in patient with kidney
transplantation.
Results of laboratory test should be available and then reviewed
within 24 hours.
Frequency of clinical visit:
2-3 /week first months 1-2 /week for 2-3 month 2-4 weeks for 4-
6 months,4-6 week weeks for 6-12 months and then 3-6
monthly.
A detailed review is needed annually.
Diagnosis of non-adherence is important and needs to prevent.
Induction immunosuppression in low risk patients includes IL2-RA and for high risk recipients includes lymphocyte depleting antibodies.
Maintenance immunosuppression includes CNI (tacrolimus is
close) and anti-proliferative agent (usually MMF unless
contraindicated) ± steroids.
-CNI levels should be checked regularly.
-Generic drugs should not be used unless being proven
bioequivalent.
Acute rejection should be diagnosed by renal biopsy.
Recipients with DGF should have protocol biopsy and SV40 and C4d staining is necessary.
In addition, anti HLA-Abs are needed to be evaluated.
The first line treatment for acute rejection consists high- dose
corticosteroids.
Refractory TCMR needs treatment by lymphocyte depleting agents (TDAs).
-ABMR treatment modalities are plasmapheresis IVIG
rituximab, TDAs or bortezomib.
Renal biopsy in needed with chronically deteriorating TX with
C4d and SV40 staining to diagnosis chronic allograft injury(CAN).
Treatment of CAN:
1- In case of evidence for CNI toxicity reduction or withdrawal of it suggested.
2- In case of evidence of immune injury immunosuppression
should be intensified.
Control of BP is suggested at each visit.
BP should be less than140/90 and in case of albuminuria or
proteinuria should be less than 130/80 mmHg.
RAAS inhibitors should be used with caution during the first
3 months.
Hyperlipidemia is suggested to be evaluated and control to
reduce CVD risk.
PTDM should be diagnosed and treated appropriately.
Appropriate treatment for IHD in suggested.
Smoking should be stopped after the transplantation.
All recipients should follow a healthy lifestyle including a healthy diet, ideal body weight, appropriate physical activity, avoidance of alcohol over the counter or herbal medicine consumption.
Cancer screening is suggested for all recipients.
Annual influenza vaccine is recommended.
CMV prophylaxis is recommended for the first 3-6 month and 6 weeks after TDA usage.
Appropriate diagnosis and treatment for CMV is suggested.
Screening for EBV is suggested for high risk (D+/R-) recipients.
Screening for BK virus nephropathy and treatment by immunosuppression is recommended.
Oral prophylaxis for pneumocystis jirovecii and proper treatment with cotrimoxazole is suggested.
Osteoporotic recipients are considered for steroid-avoidance immunosuppression.
Appropriate treatment for hyperthyroid is suggested.
ACEIs or ARBs are Recommended for post TX polycythemia.
One-year wait is suggested before conception in TX recipients.
MMF and m-TORi should be stopped before conception.
Sexual dysfunction should be evaluated and treated.
· The level of evidence is 5 for guidelines.
Summary of Clinical Practice Guidelines for the Post-Operative Care of the Kidney Transplant Recipient
Organisation of Outpatient Follow-up
Clinic infrastructure
We suggest that the following infrastructure should be in place for KTR follow up (2D):
A consultant-level health care professional should be available for every transplant clinic
KTRs should be reviewed in a dedicated outpatient area
1. The results of blood tests (including drug levels if possible) should be available within 24 hours
2. A formal mechanism should exist for results review by health care professionals within 24 hours of a clinic appointment
3. There should be access to a multidisciplinary renal team including pharmacist, dietician, social worker and psychologist
4. Patient care should be planned along principles set out in the National Service Framework and “Kidney Health Delivering Excellence”
KTR: Clinic frequency
We suggest that uncomplicated patients may be reviewed progressively less frequently (2C)
• 2-3 times weekly for the first month after transplantation
• 1-2 times weekly for months 2-3
• Every 2-4 weeks for months 4-6
• Every 4-6 weeks for months 6-12
• 3-6 monthly thereafter
KTR: Patient access
We suggest that all patients should have access to support services and results. (2C)
1. All patients should have the option of on-line access to their results via the “Patient View” service
2. All patients should have open access to the renal transplant outpatient service and have an established point of contact for enquiries
3. Patient information should be available in both written and electronic formats
KTR: Chronic transplant care review
We suggest that a detailed review should be performed annually post-operatively (2C)
Kidney Transplant Recipient: Non-adherence
We suggest that it is important to prevent and detect non-adherence in kidney transplant recipients. (2C)
Kidney Transplant Recipient: Immunosuppressive treatment –
We recommend that the patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression (1D)
Induction immunosuppression
We recommend induction therapy should take into account the following:
Maintenance immunosuppression
Monitoring of immunosuppression
We suggest that long-term monitoring of immunosuppression levels is required as follows:
Prescribing and the use of generic agents ;
Diagnosis of acute rejection
Treatment of acute rejection
Diagnosis of Chronic Allograft Injury
Treatment of chronic allograft injury
Renal biopsy in chronic allograft injury
We suggest that a renal transplant biopsy is indicated:
Kidney Transplant Recipient: Cardiovascular Disease and Lifestyle
Hypertension
Dyslipidaemia
Diabetes mellitus
Ischaemic heart disease
We suggest that KTRs receive standard treatment for ischaemic heart disease, including thrombolysis, revascularisation, and secondary prevention (2C)
Smoking cessation
We recommend that smoking should be strongly discouraged in transplant recipients (see guideline 6.4) (1A)
: Lifestyle measures
Cytomegalovirus (CMV) disease Guideline
Prophylaxis and treatment of CMV disease
We recommend:
Epstein Barr Virus (EBV) infection
Varicella Zoster Virus (VZV) infection :
Herpes Simplex Virus (HSV) infection
We recommend:
: BK virus (BKV) nephropathy
Haematological Complications Anaemia
We suggest that chronic anaemia should be managed in the same way as other patients with CKD (2D)
Level v
The BTS guideline detailed all aspects of acute and chronic management of kidney transplant recipient. By elaborating on assessment of adherence , induction and maintenance therapy, highlighting on high and low risk profile patients. Vaccinations and treatment of acute and chronic rejections and elucidating the updated management of other medical conditions complicating kidney transplantation such as infection, hypertension and diabetes mellitus.
Immunosuppression for kidney transplanted patients:
Induction:
Biologic agents are recommended for induction therapy before or the time of transplantation.
For high immunologic risk patients ,T- lymphocyte depleting antibodies is recommended.
For low immunologic risk patients, IL-2 receptor antagonist is indicated.
T-lymphocyte depleting antibodies may be considered in calcineurin inhibitors CNi or steroid withdrawal or avoidance protocols.
Maintenance protocol:
has to contain CNi and anti-proliferative agent in addition to corticosteroid which might be avoided or withdrawn after first week post transplantation in low and moderate risk patients.Its not recommended to withdraw steroid if it continued to be in use after the first month. However , its recommended to consider steroid inclusive protocol in high immunologic risk patients.
Its recommended to introduce Tacrolimus as the CNi of first choice with trough blood level of 4-8 ng/ml. An alternative to Tacrolimus in case of complicating side effects is Cyclosporin .Lowest trough level is recommended after 3 months post operatively.
Mycophenolic acid is Drug of choice as anti-proliferative , superior to Azathioprin, unless patient is not willing to consider anti-conception measures and increasingly prone to have pregnancy, then Azathioprime is indicated .there is no difference between Mycophenolate Sodium and Mycophenolate Mofetil regarding clinical profile.
The Guideline addressed thoroughly the follow up and frequency of checking for trough level and renal function as per the time duration and necessity.
Rejection :
Was discussed elaborately regarding risk factors, diagnosis and treatment. furthermore, different types of acute rejections, TCMR and ABMR diagnostic criteria was showcased. Moreover, histologic criteria and importance of C4d was demostrated.
Treatment for TCMR including first line of methylprednisolon and second line ATG was discussed in details.
For ABMR with its complicated presentation and diagnostic criteria , the guideline detailed the management points with Plasmapharesis , Retuximab, IVIg, Bortezomibe and Eculizumab.
Chronic Rejection:
was reviewed in depth , demonstrating the best tool to diagnose and manage thoroughly.
The summary of clinical practice guidelines for the post-operative care of the kidney transplant recipient
Kidney transplant recipient (KTR): Organization of outpatient follow-up
KTR: Clinic infrastructure
The transplant clinic should follow the following requirements:
KRA: Clinic frequency
Patients need to be followed up as follows:
KTR: Patient access
The patients should have access to support services and results. Their information should be available to them in written and electronic formats.
KTR: Chronic transplant care review
A detailed review should be performed annually after the procedure, and it should be facilitated by a health care professional and it should address medical, social, psychological and sexual areas. The patients should have ready access to a renal dietician, social worker, pharmacist and psychologist.
KTR: Non-adherenceKTR: Recognizing non-adherence
Factors associated with non-adherence should be identified and a pathway should be in place for patients as at high-risk of non-adherence.
KTR: Immunosuppressive treatment KTR: Immunosuppressive regimen
The patient, the patient’s caregiver and the health care provider should engaged in the discussion process. Immunosuppressive therapy includes:
1. Induction immunosuppression
2. Maintenance immunosuppression
KTR: Acute rejection A transplant biopsy should be carried out without delay to diagnose acute rejection. Obtaining two cores, with a 16 guage biopsy needle will increase the sensitivity of the investigation.
For acute cellular rejection, high does intravenous corticosteroids are the first-line of treatment, progressing to maintenance doses. Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection.
For antibody mediated rejection (AMR), steroids, plasma exchange, intravenous immunoglobulin, anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib may be used.
The immunosuppression should be adjusted after an episode of acute rejection.
KTR: Chronic Allograft injury Early identification and diagnosis allows for a better prognosis of the graft. Serial monitoring of the patient’s serum creatinine, urine protein or albumin:creatinine ratio (ACR) should be performed. A renal biopsy is the investigation of choice to elicit the cause of the dysfunction. During this time, a serum sample should be taken to look for HLA-specific antibodies.
If the cause is CNI toxicity, the CNI should be withdrawn. Immunosuppression doses should be optimized if there is ongoing immune injury.
The indications of a renal biopsy include:
Persistent increase in serum creatinine which cannot be explained by another cause
Every 7-10 days during delayed graft function (DGF)
If expected renal function is not achieved within 4-8 weeks after transplantation
Sustained new onset proteinuria.
KTR: Cardiovascular disease and lifestyle The management of hypertension is crucial. The blood pressure should be regularly monitored and should be <140/90 mmHg in clinic.
Fasting lipid levels should be measured annually for KTR, and the treatment targets should be similar to those of the general population. The choice of medication should account for the concurrent immunosuppression medications.
Screening for the development of port-transplant diabetes mellitus (PTDM) should be done at each clinic visit. The diagnosis of PTDM is made once the patient has reached stable maintenance immunosuppression.
All KTR patients should receive the standard treatment for ischemic heart disease, including thrombolysis, revascularization and secondary prevention.
Patients receiving a renal transplantation should be encouraged to stop smoking.
Advice on a healthy lifestyle should be emphasized at every clinic visit. This includes a healthy diet, target ideal body weight, physical activity and reduced alcohol consumption.
KTR should be screened for breast, cervical, prostate, colon cancer. The patients should be aware of the malignancy risk. Non-melanoma skin cancer advice should be provided. Immunosuppression should be reduce if neoplasia develops. M-TORs have specific anti-tumor effects in Kaposi sarcoma.
KTR: Infection complicationsThe patients should be vaccinated with inactivated viruses and influenza annually. They should not receive live attenuated vaccines. Hepatitis B surface antibody levels should be checked annually, if the titres fall below 10 mIU/mL, the patient should be revaccinated. A pneumococcal vaccine booster should be provided every 5 years.
Prophylaxis for CMV should continue for 3-6 months, and treatment should be administered for 6 weeks after treatment with a TDA. The first line treatment for severe CMV infection is intravenous ganciclovir is used. For mild to moderate disease, oral valganciclovir can be used. The treatment duration should depend on the viral load.
EBV viral load should be monitored regularly, and immunosuppression should be reduced if EBV titres rise significantly.
Primary, uncomplicated or disseminated VZV infection should be treated with intravenous acyclovir or oral valaciclovir. Immunosuppression doses should be adjusted.
HSV systemic infection should be treated with intravenous acyclovir for at least 14 days and reduction in immunosuppression.
BK nephropathy should be screened when renal function deteriorates due to an unexplained reason. Urine microscopy should be used to screen for BK virus (BKV), and biopsy should be done to diagnose BKV. There is no definitive treatment, but immunosuppression should be reduced.
All patients with confirmed pneumocystis jirovecii infection (from respiratory secretions) should be treated for 14- 21 days with co-trimoxazole, or pentamidine. For patients with severe disease, consider additional glucocorticoid therapy.
For prophylaxis pf PJP, all patients should receive 3-6 months of co-trimoxaole treatment after the surgery, oral anti-fungal medication for a week and isoniazid with pyridoxine 6 months after transplantation.
All blood components should be for hepatitis E.
KTR: Bone and joint diseasePatients high at risk for osteoporosis should avoid the use of steroids. Severe hypoparathyroidism should be treated prior to the surgery. Hyperuricemia should be managed with colchicine, allopurinol should be avoided when using azathioprine. Reduced doses of CNIs should be considered in patients suffering from intractable bone pain caused by CNIs.
KTR: Hematological complicationsAnemia should be managed as per CKD patient guidelines. Polycythemia should be treated with angiotensin converting enzyme inhibitors or angiotensin receptor blockers, venesection in refractory cases. Hemoglobin should be monitored at every clinic visit.
KTR: Reproductive issues MPA-containing immunosuppressant medications and m-TORi should be stopped prior to conception and replaced appropriately. Conception should be attempted after at least one year of transplantation.
Counsellors and the obstetric teams should be involved. Aspirin 5mg daily from 12 weeks of gestation until the birth should be initiated to reduce the risk of pre-eclampsia.
Male patients should be counselled that m-TORi may reduce sperm count.
Summary of audit measures for the post-operative care of the kidney transplant recipient
1. Kidney Transplant Recipient (KTR):
The organisation of Outpatient Follow-up includes good clinic infrastructure ensuring the availability of health care professionals. Clinic frequency suggests that uncomplicated patients may be reviewed progressively in regular intervals. All patients should have access to support services and results.
2. Kidney Transplant Recipient: It is important to prevent, detect and take necessary action towards non-adherence in kidney transplant recipients.
3. Kidney Transplant Recipient:
Immunosuppressive treatment
· Induction immunosuppression therapy should take into account the following: Immunosuppressive drugs should be started before or at the time of renal transplantation.
· Induction therapy with biological agents should be administered to all KTRs. In patients at low immunological risk, this will generally involve an interleukin-2 receptor antagonist (IL2-RA) and higher immunological risk may be considered for T-cell (lymphocyte) depleting antibodies (TDAs)
· Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance.
· CNI should be started at the time of transplantation and not delayed until the graft is functioning.
· Maintenance immunosuppression should normally consist of a calcineurin inhibitor (CNI) and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs.
· Mycophenolic acid-based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception.
· KTRs who are unable to tolerate tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second-line agents such as ciclosporin, sirolimus, everolimus, or belatacept.
· Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological-risk kidney transplant recipients.
if any signs of rejection, failure, opportunistic infection, need for graft biopsy, treatment (ABMR, cellular mediated), chronic rejection, allograft nephropathy if any progressive disease treats chronic kidney disease failure consequences accordingly.
The article deals with guidelines for the care and follow-up of kidney transplant recipients (KTRs) post-operatively.
Guideline 1: A dedicated outpatient (OP) area with a consultant, having facilities for receiving blood reports within 24 hours and reviewing them within 24 hours should be available. The patients should be able to access services online and should be able to contact OP services via a single point of contact. The patient should be under close follow-up with graded gap in follow-up visits with time. The OP clinic should be patient-centric with presence of specialists involving multiple domains of patient care and should perform a detailed annual review.
Guideline 2: Patients more prone to non-adherence should be identified and managed pre-emptively.
Guideline 3: Patient and care-giver should be involved in selecting induction and maintenance immunosuppression.
Induction therapy should be started at time of transplantation. Low-risk patients can be induced with IL2 receptor antagonists while those with steroid sparing or CNI sparing regime as well as high-risk patients could be induced with T-cell depleting antibodies (TDAs). Maintenance immunosuppression should include a calcineurin inhibitor – CNI (preferably tacrolimus), which should be started at time of transplant, an anti-proliferative agent (mycophenolate – MPA preferred over azathioprine except in females planning to conceive), with or without (in low-risk patents) corticosteroids. Generics should be used only if their bioequivalence has been proved. CNI levels should be monitored regularly, especially when changing doses or formulation.
Guideline 4: A transplant kidney biopsy, 2 cores using a 16-gauge biopsy needle and staining with C4d and SV40, with DSA testing should be done before treating an acute rejection. Protocol biopsy should be done in persisting delayed graft function.
High dose intravenous corticosteroids should be given for acute cellular rejection (ACR), while refractory or aggressive vascular rejection will require TDAs. Antibody mediated rejection (AMR) will require one or more of steroids, plasma exchange, IVIG, anti-CD 20 antibody, TDAs or bortezomib. Post-rejection, azathioprine should be changed to MPA, dose of MPA should be maximized and steroids added if on steroid-free regimen.
Guideline 5: Early identification of graft injury can be done by monitoring of renal function (creatinine and proteinuria) on each follow-up visit. In presence of graft dysfunction or sustained new-onset proteinuria, a renal biopsy with DSA testing should be done. Treatment of graft dysfunction as per the etiology should be done (CNI withdrawal in case of CNI toxicity, and immunosuppression intensification in case of ongoing immune injury).
Guideline 6: BP should be measured on each follow-up visit and controlled using antihypertensives. Causes of resistant hypertension should be evaluated and treated. Annual lipid profile testing should be done and dyslipidemia should be treated, especially in those with cardiovascular risk using statins. Screening for post-transplant diabetes mellitus (PTDM) should be done at each follow-up visit and should be managed with consultation of endocrinologist. Regular screening for diabetic complications should be done. Ischemic heart disease should be managed as per standard protocols. Smoking cessation, maintaining a healthy lifestyle with regular physical activity, and maintaining weight should be encouraged.
Guideline 7: Patients should be made aware about risks of malignancies and screened for skin, cervical, breast, colon, and prostate cancer, Self-examination for detection of cancers should be taught. Skin examination by specialist should be done every 6 months for 5 years and then annually. For non-melanoma skin cancer (NMSC), patients should be taught above avoiding direct sunlight exposure and use of sunblock. If neoplasia develops, immunosuppression reduction with use of mTOR inhibitors in de novo malignancy is suggested (especially in Kaposi sarcoma).
Guideline 8: Vaccination with inactivated viruses should be done, including annual influenza vaccination, pneumococcal vaccine (every 5 years) and hepatitis B virus vaccination if anti HBsAb levels are low. Pre-transplant donor and recipient serology for CMV and EBV should be recorded. CMV prophylaxis should be given for 3-6 months post-transplant, and for 6 weeks after use of TDAs. CMV infection can be treated using oral valganciclovir or intravenous ganciclovir (in life-threatening disease). In presence of post-transplant lymphoproliferative disease (PTLD), immunosuppression should be reduced or stopped. EBV viral load should be monitored after treatment of rejection. Varicella zoster virus (VZV) infection treatment will require oral acyclovir or valaciclovir with immunosuppression reduction during infection. Herpes Simplex Virus (HSV) infection should be treated with oral or intravenous acyclovir with reduction of immunosuppression during infection, with prophylaxis in case of recurrent infections. BK virus nephropathy screening using urine examination and PCR on serum/ urine should be done in case of unexplained graft dysfunction, and can be confirmed by a kidney biopsy. Treatment requires reduction in immunosuppression. Pneumocystis jirovecii prophylaxis with co-trimoxazole for 3-6 months post-transplant should be given. Confirmed infection should be treated with oral or intravenous co-trimoxazole (if contra-indicated, use pentamidine) for 14-21 days, with adjunctive glucocorticoids in severe disease. Oral antifungal prophylaxis should be given for 1 week post-transplant, and in latent TB INH with pyridoxine for 6 months should be given.
Guideline 9: KTRs with or at high risk of osteoporosis should be screened with DEXA scan, and considered for steroid-avoiding regimen. Osteoporosis should be treated as per guidelines. Severe hyperparathyroidism should be treated pre-transplant and cinacalcet can be used in KTRs. Gout in KTR can be treated using colchicine and brief course of oral prednisolone in case of acute gout. NSAIDs should be avoided. Febuxostat and allopurinol should not be used with azathioprine. In intractable bone pains, CNI reduction or withdrawal and dihydropyridine calcium channel blocker use should be considered.
Guideline 10: Anemia should be treated as per management of anemia in CKD. Polycythemia should be treated (if hematocrit is >52% in men and >49% in women) using ACEi or ARBs and venesection in refractory cases.
Guideline 11: Before attempting conception, KTRs should have a stable graft function for 1 year after transplant and MPA as well as mTOR inhibitors should be replaced. Pre-transplant and post-transplant counselling regarding fertility and contraception should be provided to both the female KTRs and their partner. Pregnancy should be managed with multidisciplinary approach. Aspirin should be started from 12 weeks of gestation till delivery, if not contraindicated. Breastfeeding risks and benefits should be discussed with the KTR. Male KTRs should be explained about theoretical teratogenic risk with MPA and reduced sperm counts with mTOR inhibitor use (hence to be avoided in patients wishing to maintain fertility or replace prior to conception). Sexual dysfunction should be enquired into and managed. Sildenafil can be used if KTR is not on nitrates.
2. What is the evidence provided by this article?
The level of evidence is level 5 – guidelines
Summarise this article
Introduction: after kidney transplantation the post operative care of the recipient is mandatory, this article figure out the guide line in patient care, prevention of acute rejection, optimization of graft function and prevention of opportunistic infection, preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression – malignancy, infection and premature cardiovascular disease.
Kidney Transplant Recipient (KTR): Organisation of Outpatient Follow-up:
– The recipient should be reviewed in a dedicated outpatient area, by a consultant level health care professional (2D).
– The blood test result should be available within 24 hours (2D).
– There should be access to a multidisciplinary renal team including pharmacist, dietician, social worker and psychologist (2D).
– Clinic visit frequency (2C):
· 2-3 times weekly for the first month after transplantation.
· 1-2 times weekly for months 2-3.
· Every 2-4 weeks for months 4-6.
· Every 4-6 weeks for months 6-12.
· 3-6 monthly thereafter.
– Patient access (2C):
· Open access to the renal transplant outpatient service with ease of contact for enquiries
· Patient information should be available in both written and electronic formats.
– Chronic transplant care review(2C): Annual patient review, patient centered clinic with concerns in medical, social, psychological and sexual domains, and an Access to a renal dietician, social worker, specialist renal pharmacist and/or psychologist should be readily available from this clinic.
Kidney Transplant Recipient: Non-adherence (2C):
· Factors associated with non-adherence should be identified.
· An established interventional pathway should be in place for those at high risk of or with proven nonadherence.
· Pathways should be in place for paediatric KTRs in transition and for adolescent KTRs.
Immunosuppression regimen
Induction immunosuppression
KTR: Maintenance immunosuppression
Prescribing and the use of generic agents
Diagnosis of acute rejection
Treatment of acute rejection
Diagnosis of Chronic Allograft Injury
Detection of Chronic Allograft Injury
Diagnosis of Chronic Allograft Injury
Treatment of chronic allograft injury
Renal biopsy in chronic allograft injury
Hypertension
Dyslipidemia
Diabetes mellitus
Ischemic heart disease
Smoking cessation
Lifestyle measures
Screening for cancer
Non-melanoma skin cancer
Immunosuppression in cancers
Vaccination
Prophylaxis and treatment of CMV disease
EBV infection
VZV infection
HSV infection
BK nephropathy
Pneumocystis jirovecii infection – treatment and prophylaxis
Post-transplant infection prophylaxis
Hepatitis E Virus
Osteoporosis
Tertiary hyperparathyroidism
Treatment of gout
Calcineurin inhibitor bone pain
Anaemia
Polycythaemia
Conception and contraception
Sexual dysfunction
What is the evidence provided by this article?
Level of evidence I – guidelines
Post-Operative Care in the Kidney Transplant Recipient (BTS GUIDELINES- 2017)Introduction:
These guidelines for the period post renal transplantation the management of kidney transplantation divided into two phases:
1. An early post-operative phase when prevention of acute rejection, optimization of graft function and prevention of appropriate infection
2. Late phase to preserve good graft function after transplantation
Summary of clinical practice guidelines:
· KTR clinic infrastructure constant level after result of blood test should be variable within 24 hours
· Access to multi- disciplinary renal team including pharmacist, dietician, social worker and psychiatrist
· Clinic frequency
· 2-3 weekly for the first month after transplantation
· 1-2 time weekly for 2 to 3 months
· Every 2-4 weeks for 4-6 months
· 4-6 week for 6-12 months
· KTR patient should have a single result renal transplant service and ==information should available both written and electronic
· Chronic transplant care review
· KTR recognizing ban-Adherence should identified factors for non-adherence and interventional pathway for high-risk transplant recipient
Kidney transplant recipient: immunosuppressive treatment
Patients should be engaged in the dissection around selection of indication agent and maintenance immunosuppression
Induction therapy:
Interleukin-2 receptor antagonist for low immunological risk recipient
T-cell lymphocyte depleting antibodies for higher immunological risk.
KTR induction immunosuppressive
CNI should be started at the time of transplantation (2c)
Maintenance immunosuppression in KTR consist of CNI, antiproliferative agent with or without corticosteroid in low and reducing immunological risk KTRs
Tacrolimus trough level 4-8 ng/ml in low and medication
Immunological risk are not at risk of develop PTD(2c)
Mycophenolate acid-based regimen be the first anti-==performance to Azathioprine except futile KTRs are unwilling to use contraception(2B)
Slow-release TAC second line for whom had side effects to peak dose toxicity(2C)
KTRs who are unable to tolerate tacrolimus or who suffer a serious adverse reactions to it is use to be considered second-line agents such as ciclosporin sirolimus, everolimus (B1)
Steroid avoidance or withdrawal can be used during the first week after transplantation in low immunological-risk kidney transplant recipients (2B)
Minimum target levels for CNI in uncomplicated renal transplantation after 3 months (2c)
Steroid unknown regimen should be a low dose (prednisolone 5mg per day or less) (2c)
Maintain of TAC and cyclosporin if:
· Medication interaction
· Dosage change
· Unexplored graft function (2c)
· Mycophenolic acid co level uncertain (2D)
· Sirolimus should be monitored by the co trough level(2c)
· Immunosuppression drug should be prescribed by brand name (2D)
A transplant kidney biopsy should be carried out before treating acute rejection episodes(1C).
Recommended high-dose corticosteroids should be the first-line treatment for acute cellular rejection(1D).
Restarted steroid in steroid-free patients with an acute rejection of any type (2D).
Suggest that lymphocyte-depleted agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection B or T 4 type II or type III (2 C).
We suggest that antibody-mediated rejection (AMR) should be treated with one or more of the following medications: steroids, plasma exchange, and intravenous immunoglobulin.
Anti-CD 20 antibodies, lymphocyte-depleting antibodies or bortezomib (2C).
After an episode of rejection (unless associated with lower CNI levels)
Azathioprine should be switched to MPA-based immunosuppression, MPA should be started or the existing dose of MPA maximized(2D)
We suggest that renal biopsy patients with critical deterioration function should be stained for C4d and SV40(2C).
Chronic allograft type should be treated by the withdrawal of calcineurin inhibitor if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy(2C)
Intensification of immunosuppression if there is evidence of ongoing immune injury.
Treat as CKD
Indication of kidney transplantation renal biopsy in chronic allograft injury:
Sustained new onset proteinuria develops PCR > 50/mg/mmol, an ACR>35mg/mmol (2 C)
If expected renal function is not achieved within 4-8 weeks(2D)
Every 7-10 days during delayed graft function (2C)
Persistent unexplained elevation of creatinine or failure to return to the baseline after an episode of biopsy prevents acute rejection BPAR (1C)
Hypertension:
BP clinically should be <140/90 mmHg.
Renin-angiotensin system may be more effective in the minimization of proteinuria but should be used with caution in the first 3 months post-transplant (2C).
The choice and dose of start in kidney transplantation dyslipidaemia should take into account immunosuppression high dose ≥ 40 mg sampling should be avoided combination with cyclosporin and calcium channel antagonist (2D).
The diagnosis of PTDM is made based WHO criteria for the diagnosis of DM.
The treatment target of dyslipidaemia in kidney transplantation should be the same in the general population (2C)
The diagnosis of DM is based on fasting or random blood, serum HA1c or oral GTT(1c).
Screening for cancer in kidney transplant patients should be similar to the general population for cervical, breast, colon and prostate cancer.
Kidney transplant patients with non-melanoma skin cancer.
C1: colchicine can be used for gout in kidney transplant patients (2D)
Kidney transplant patients recommended that MPA continuing immunosuppression drugs should be stopped prior to conception and replaced appropriately (1 A)
Kidney transplantation recognizing non-adherence is important to prevent and detect non-adherence in kidney transplant recipients (2C).
Kidney transplantation induction immunosuppression:
CNI should be started at the time of transplantation and not delayed until the graft is functioning (2C).
Maintenance immunosuppression kidney transplantation suggests avoiding steroid withdrawal during the first week after transplantation (2B).
Kidney transplantation: mainly if tacrolimus and cyclosporine levels should be maintained. TAC is co trough level and cyclosporin co or C2 is the post dose C2
Kidney transplantation vaccination should not receive live attenuated vaccines (2C).
Prophylaxis should continue for 3-6 months (1B)
Treatment should be given for 6 weeks after treatment with a TDA (1C).
In kidney transplantation: EBV we recommended that immunosuppression should be reduced or stopped following the development of post-transplant==
Kidney transplantation and infection:
Disseminated, ocular or invasive shingles should be treated with intravenous acyclovir until the lesion is scaly covered with a reduction in immunosuppression (1B)
Kidney transplantation: B/L nephropathy should be treated by reduction in immunosuppression(1D).
Kidney transplantation: pneumocystis juroveci infection prophylaxis should be for 3-6 months of treatment with co-trimoxazole 480 mg daily for pneumocystis jureveci prophylaxis following renal transplantation (1B).
Kidney transplantation for osteoporosis on long-term steroids or at high risk for osteoporosis should undergo Dexa-Scanning if GFR >30 ml/min/1.73m2 (2D).
Tertiary hyperparathyroidism should be treated before transplantation (2D)
Cinacalcet can be used in kidney transplantation (2C)
Kidney transplantation treatment of giant. We recommended that neither allopurinol nor febuxostat should with azathioprine (1c)
A transplant kidney biopsy should be carried out before treating acute rejection episodes(1C).
Recommended high-dose corticosteroids should be the first-line treatment for acute cellular rejection(1D).
Restarted steroid in steroid-free patients with an acute rejection of any type (2D).
Suggest that lymphocyte-depleted agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection B or T 4 type II or type III (2 C).
We suggest that antibody-mediated rejection (AMR) should be treated with one or more of the following medications: steroids, plasma exchange, and intravenous immunoglobulin.
Anti-CD 20 antibodies, lymphocyte-depleting antibodies or bortezomib (2C).
After an episode of rejection (unless associated with lower CNI levels)
Azathioprine should be switched to MPA-based immunosuppression, MPA should be started or the existing dose of MPA maximized(2D)
We suggest that renal biopsy patients with critical deterioration function should be stained for C4d and SV40(2C).
Chronic allograft type should be treated by the withdrawal of calcineurin inhibitor if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy(2C)
Intensification of immunosuppression if there is evidence of on going immune injury.
Treat as CKD
Indication of kidney transplantation renal biopsy in chronic allograft injury:
Sustained new onset proteinuria develops PCR > 50/mg/mmol, an ACR>35mg/mmol (2 C)
If expected renal function is not achieved within 4-8 weeks(2D)
Every 7-10 days during delayed graft function (2C)
Persistent unexplained elevation of creatinine or failure to return to the baseline after an episode of biopsy prevents acute rejection BPAR (1C)
Hypertension:
BP clinically should be <140/90 mmHg.
Renin-angiotensin system may be more effective in the minimization of proteinuria but should be used with caution in the first 3 months post-transplant (2C).
The choice and dose of start in kidney transplantation dyslipidaemia should take into account immunosuppression high dose ≥ 40 mg sampling should be avoided combination with cyclosporin and calcium channel antagonist (2D).
The diagnosis of PTDM is made based WHO criteria for the diagnosis of DM.
The treatment target of dyslipidaemia in kidney transplantation should be the same in the general population (2C)
The diagnosis of DM is based on fasting or random blood, serum HA1c or oral GTT(1c).
Screening for cancer in kidney transplant patients should be similar to the general population for cervical, breast, colon and prostate cancer.
Kidney transplant patients with non-melanoma skin cancer.
C1: colchicine can be used for gout in kidney transplant patients (2D)
Kidney transplant patients recommended that MPA continuing immunosuppression drugs should be stopped prior to conception and replaced appropriately (1 A)
Kidney transplantation recognizing non-adherence is important to prevent and detect non-adherence in kidney transplant recipients (2C).
Kidney transplantation induction immunosuppression:
CNI should be started at the time of transplantation and not delayed until the graft is functioning (2C).
Maintenance immunosuppression kidney transplantation suggests avoiding steroid withdrawal during the first week after transplantation (2B).
Kidney transplantation: mainly if tacromulus and cyclosporine levels should be maintained. TAC is co trough level and cyclosporin co or C2 is the post-dose C2
Kidney transplantation vaccination should not receive live attenuated vaccines (2C).
Prophylaxis should continue for 3-6 months (1B)
Treatment should be given for 6 weeks after treatment with a TDA (1C).
In kidney transplantation: EBV we recommended that immunosuppression should be reduced or stopped following the development of post-transplant==
Kidney transplantation and infection:
Disseminated, ocular or invasive shingles should be treated with intravenous acyclovir until the lesion is scaly covered with a reduction in immunosuppression (1B)
Kidney transplantation: B/L nephropathy should be treated by a reduction in immunosuppression(1D).
Kidney transplantation: pneumocystis juroveci infection prophylaxis should be for 3-6 months of treatment with co-trimoxazole 480 mg daily for pneumocystis jureveci prophylaxis following renal transplantation (1B).
Kidney transplantation for osteoporosis on long-term steroids or at high risk for osteoporosis should undergo Dexa-Scanning if GFR >30 ml/min/1.73m2 (2D).
Tertiary hyperparathyroidism should be treated before transplantation (2D)
Cinacalcet can be used in kidney transplantation (2C)
Kidney transplantation treatment of giant. We recommended that neither allopurinol nor febuxostat should be with azathioprine (1c)
evidence level 5
Post-Operative Care in the Kidney Transplant Recipient Introduction
KTR management is broken into two phases:
A. an early post-operative phase to prevent acute rejection, optimize graft performance, and prevent opportunistic infection
1. Preventing acute rejection, optimizing graft function, and preventing opportunistic infection in the early post-operative phase
2. Preserving good graft function, ensuring medication adherence, and preventing immunosuppression’s long-term effects of malignancy, infection, and premature cardiovascular disease in the later phase
Summary of Clinical Practice Guidelines for Kidney Transplant Recipient Post-Operative Care
Kidney Transplant Recipient (KTR): Outpatient Follow-up Organization
KTR: Clinic infrastructure · Consultants should cover every transplant clinic · KTRs should be assessed in a dedicated outpatient area · Blood test results should be available within 24 hours · A multidisciplinary renal team should include a pharmacist, dietitian, social worker, and psychologist.
KTR: Clinic frequency simple individuals may be evaluated progressively less frequently (2C)
2-3 times a week during the first month after transplantation, then 1-2 times a week. 2-3 weeks per month for months 4-6 weeks per month for months 3-6 monthly after 6-12
KTR: All patients should have access to results and support services. (2C)
KTR: Annual post-operative chronic transplant care review (2C)
Non-adherence in kidney transplant recipients
KTR: Kidney transplant recipients must be monitored for non-adherence. (2C)
3. Kidney Transplant Recipient: Immunosuppressive therapy
The patient and caregiver should choose the induction agent and immunosuppressive maintenance (1D)
KTR: Induction immunosuppression
All KTRs should receive induction therapy with biological agents and immunosuppressive medications before or during kidney transplantation (1B).
1) an interleukin-2 receptor antagonist (IL2-RA) for low immunological risk people.
2) Higher immunological risk T-cell (lymphocyte) depleting antibodies (TDAs).
Lower immunological risk patients who want to avoid steroids or calcineurin inhibitors (CNIs) may benefit from TDA induction therapy. (1C)
KTR: Induction immunosuppression
· A CNI should be started immediately after transplantation, not after the graft is functional (2C)
KTR: Immunosuppression maintenance
· should normally consist of a CNI and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs (1B). In patients taking steroids who are low and medium immunological risk and not at high risk of post transplant diabetes mellitus (PTDM), tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice (2C)
Mycophenolic acid-based medications should be the first-line anti-proliferative treatment instead of azathioprine, except in fertile KTRs who refuse contraception. (2B
If peak dosage toxicity adverse effects are unacceptable, slow-release tacrolimus may be a second-line treatment (2C)
· the use of second-line medications such ciclosporin, sirolimus, everolimus, or belatacept if tacrolimus was not tolerated · MPA-based therapies should be the first-line antiproliferative agent, in preference to azathioprine, except in fertile KTRs who are unwilling to utilize reliable contraception (2B)
MMF and enteric-coated mycophenolate sodium provide comparable maintenance immunosuppression (2B)
In low immunological risk kidney transplant recipients, steroid avoidance or withdrawal might be employed during the first week after transplantation (2B)
· minimal target levels for CNIs in uncomplicated renal transplantation after 3 months · CNIs should not be removed (2B) · if steroids are not withdrawn during the first month, then they should be kept at low dose (prednisolone 5 mg per day or less) (2C)
KTR: Immunosuppression monitoring Tacrolimus and ciclosporin levels should be tested three times a week initially, and if: 1) a new medicine is administered 2) 2) the composition or dosage is altered
3) unexplained graft malfunction · Tacrolimus and ciclosporin levels should be provided within 24 hours of blood samples in the first three months after transplantation · Sirolimus should be monitored by the C0 trough level
4. Kidney Transplant Recipient: Acute rejection
KTR: Diagnosis of acute rejection · a transplant renal biopsy should be done before treating an acute rejection episode unless this will delay treatment or pose a significant risk to the patient · two cores of renal tissue should be obtained at transplant biopsy · a 16-gauge automated core biopsy needle is recommended · a protocol transplant renal biopsy is recommended for persisting delayed graft function · routine C4d and C4dx should be done
KTR: Treatment of acute rejection · high-dose intravenous corticosteroids should be the first-line treatment for acute cellular rejection · maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type · lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e., Banff category 4 Type II and III) · AMR should be treated steroids; plasma exchange; IVIG; anti-CD20 antibody, lymphocyte-depleting antibody, or bortezomib · following an episode of rejection (unless linked with low CNI levels) – switch to MPA-based immunosuppression, start MPA, or increase MPA dose.
5. Kidney Transplant Recipient: Chronic Allograft Injury · C4d and SV40 should be stained on renal biopsies in individuals with continuously decreasing function.
KTR: Treatment of chronic allograft injury · By withdrawing calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy · By intensifying immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection) · In a manner similar to other patients with chronic kidney disease (CKD), following similar preventative strategies and wit
KTR: Renal biopsy in chronic allograft damage. Indicated if: · a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection · every 7-10 days during delayed graft function (DGF) · if expected renal function is not achieved within 4-8 weeks · if sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol)
6. Kidney Transplant Recipient: Cardiovascular Disease and Lifestyle KTR: Hypertension · Blood pressure should be measured at each clinic appointment and should be <140/90 mmHg in clinic · There is no evidence that any antihypertensive drug is better than another · RAS inhibitors may be more successful in treating proteinuria · Resistant hypertension may be caused to transplant renal artery stenosis and should be examined.
KTR: Dyslipidaemia · Fasting lipid levels should be measured annually and treated as in the general population · KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease · High-dose simvastatin (>40mg daily) should be avoided in conjunction with ciclosporin and/or calcium channel antagonists
Diabetes mellitus
Dipstick urinalysis and blood sugar measurement at each clinic visit to screen for post-transplant DM (PTDM) Consider WHO criteria for DM diagnosis based on fasting or random blood, serum HBA1c, or OGTT · Once steady maintenance immunosuppression is established, PTDM can be diagnosed and managed with a diabetologist. Diabetic problems in KTR should be screened.
KTR: Ischemic heart disease · KTRs can receive typical ischaemic heart disease treatment, including thrombolysis, revascularization, and secondary prevention · transplant recipients should not smoke
KTR: Lifestyle measures · a healthy diet and body mass index (BMI) < 25 kg/m2 · limited alcohol intake and avoidance of recreational drug use · discourage the use of over-the-counter pharmaceuticals and herbal treatments.
7. Kidney Transplant Recipient: Neoplasia · Screening should be similar to the general population for cervical, breast, colon, and prostate cancer and not recommended for renal cell carcinoma · Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant · Patients with cirrhosis should undergo an annual hepatic ultrasound and determination of serum alpha fetoprotein · KTRs should be taught about the harmful effects of sun exposure and advised to cover their skin in direct sunlight and wear total sunbloc · self-examination should be encouraged with advice, at least biannual review by an up to 5 years post-transplant and annual review from 5 years · Acitretin may be used as chemoprophylaxis for patients with two or more non-melanoma skin cancers. m-TORi should be considered if neoplasia develops. m-TORs inhibit Kaposi sarcoma tumors.
Kidney Transplant Recipient: Infection Issues
KTR: Vaccination · KTRs should be vaccinated with inactivated viruses as per the normal population and receive annual influenza vaccination unless contraindicated · KTRs should have their HBsAb levels rechecked annually and be revaccinated if antibody titres fall below 10 mIU/mL · KTRs should not receive live attenuated vaccines Pneumococcal vaccine and boosters should be given to KTRs every five years.
KTR: Cytomegalovirus (CMV) illness
After TDA treatment, prophylaxis should be continued for 3-6 months until immunosuppression is lowered to long-term maintenance level.
For mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are equally effective. For life-threatening CMV disease, intravenous ganciclovir is the first-line treatment, with viral load monitoring to determine treatment duration.
KTR: Epstein Barr Virus (EBV) infection · immunosuppression should be reduced or stopped following the development of post-transplant lymphoproliferative disease (PTLD) · All high-risk (D+/R-) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year · After rejection treatment, EBV viral load should be monitored and immunosuppression reduced.
KTR: Varicella Zoster Virus (VZV) infection
· Primary infection (chickenpox) should be treated with IV aciclovir or oral valaciclovir until the lesions scab over · Uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over · Disseminated (>2 dermatomes), ocular, or invasive shingles should be treated with IV aciclovir until the lesions scab over and immunosuppression should be reduced.
Varicella-susceptible KTRs (VZV IgG negative) with primary VZV exposure should get IVIG, ideally within 96 hours but up to 10 days after exposure. If unavailable or after 10 days, oral aciclovir should be provided for seven days · Patients on the waiting list who are VZV IgG negative should be vaccinated before transplantation, and immunosuppression should be lowered during primary infection.
KTRs with recurrent Herpes Simplex Virus (HSV) infections should consider oral prophylaxis.
KTR: BK virus (BKV) nephropathy · immunosuppression should be reduced to treat confirmed BK (no specific treatment)
KTRs should be tested for BKV virus load using urine microscopy for decoy cells or PCR on urine or serum. Renal biopsy stained for SV40 should confirm suspected BK nephropathy. When serum BKV load surpasses 104 copies/ml, immunosuppression should be lowered. Patients with BK nephropathy from a previous graft can safely undergo re-transplantation.
KTR: Pneumocystis jirovecii infection – treatment and prophylaxis · Co-trimoxazole (15-20mg/kg in three or four separate doses) should be given to all patients for 14–21 days.
Patients with contraindications to co-trimoxazole should get pentamidine (4mg/kg/day intravenously) · Severe disease patients may benefit from adjunctive glucocorticoid therapy Co-trimoxazole 480mg daily for Pneumocystis jirovecii prophylaxis should be given to all renal transplant patients for 3-6 months.
KTR: Hepatitis E virus (HEV)
Hepatitis E Virus (HEV)-screened blood components should be administered to all KTR patients.
Kidney Transplant Recipient:
KTR: Osteoporosis · KTRs with osteoporosis or at high risk should be considered for steroid-avoiding immunosuppression · KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2 · Treatment should follow the Royal College of Physicians (RCP) guidelines for steroid-induced osteoporosis
KTR: Tertiary hyperparathyroidism · Treat severe hyperparathyroidism before transplantation. KTR can be treated with cinacalcet. Treatment should be the same as for other CKD patients.
KTR: Gout · neither allopurinol nor febuxostat should be given with azathioprine · Hyperuricaemia should be treated in KTRs with gout, tophi, or uric acid stones · NSAIDs should be avoided · Oral prednisolone can treat acute gout, while KTR gout can be treated with colchicine.
KTR: Bone pain inhibitor calcineurin
KTRs with intractable bone pain should consider reducing or stopping CNIs and trying dihydropyridine calcium antagonists.
Kidney Transplant Recipient (KTR): Haematological Complications • chronic anaemia should be managed the same way as other patients with CKD · polycythaemia should be treated with ACEIs or ARBs if the haematocrit surpasses 52% in men and 49% in women · refractory instances may be treated with venesection
Kidney Transplant Recipient (KTR): Reproductive Issues · MPA-containing immunosuppressants should be stopped prior to pregnancy and replaced suitably · KTRs should wait one year after transplant and have stable function before trying to conceive. m-TORi should be terminated before conception and replenished as needed. KTRs take 75 mg of aspirin daily from 12 weeks gestation till birth to minimize pre-eclampsia risk. Discuss the risks and benefits of breastfeeding. Contraception recommendations should be like the general population. Male KTRs should be aware that MPA-containing drugs may be teratogenic. KTRs should be informed that m-TORi lower male sperm count and counseled accordingly. Other than m-TORi, male KTRs can utilize all immunosuppressive medications. The danger of putative teratogenicity vs the risk of rejection when switching from MPA to azathioprine should be considered when deciding whether to continue MPA-containing drugs in a male KTR who wants to conceive. Men on m-TORi who want to conceive should quit these agents before conception and replace them as needed. Men who want to retain fertility should avoid m-TORi or bank sperm before taking these medicines. For sexual dysfunction in male KTR without nitrates, Sildenafil is safe and effective.
The BTS guidelines encompasses the duration after transplantation up to the failure of graft.
According to guidelines discussed in detail about clinical infrastructure, drugs level, frequency of visits, patient access to labs, clinic frequency, patient adherence to medication, good diet( after dietician counseling), if any concern psychologist opinion, immunosuppression doses according to trough level, prophylactic drug starting ang stopping according to region of frequency of infections.
If any signs of rejection, failure, opportunistic infection, need of graft biopsy, treatment (ABMR, cellular mediated), and chronic rejection, allograft nephropathy, if any progressive disease treat chronic kidney disease failure consequences accordingly.
Post-Operative Care in the Kidney Transplant Recipient
These guidelines cover the period after renal transplantation, specifically from initial hospital discharge until graft failure or patient death. The management of KTR can be divided into two phases:
a. an early post-operative phase when prevention of acute rejection, optimization of graft function and prevention of opportunistic infection are paramount
b. a later phase when the aims are to preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression – malignancy, infection and premature cardiovascular disease.
1. Kidney Transplant Recipient (KTR):
Organisation of Outpatient Follow-up includes good clinic infrastructure ensuring availability of health care professionals. Clinic frequency suggest that uncomplicated patients may be reviewed progressively in regular interval. All patients should have access to support services and results.
2. Kidney Transplant Recipient: It is important to prevent, detect and take necessary action towards non-adherence in kidney transplant recipients.
3. Kidney Transplant Recipient:
Immunosuppressive treatment
· Induction immunosuppression therapy should take into account the following: Immunosuppressive drugs should be started before or at the time of renal transplantation.
· Induction therapy with biological agents should be administered to all KTRs. In patients at low immunological risk this will generally involve an interleukin-2 receptor antagonist (IL2-RA) and higher immunological risk may be considered for T-cell (lymphocyte) depleting antibodies (TDAs)
· Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance.
· CNI should be started at the time of transplantation and not delayed until the graft is functioning.
· Maintenance immunosuppression should normally consist of a calcineurin inhibitor (CNI) and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs.
· Mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception.
· KTRs who are unable to tolerate tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second line agents such as ciclosporin, sirolimus, everolimus, or belatacept.
· Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients.
4. Kidney Transplant Recipient:
Acute rejection:
Diagnosis of acute rejection: Renal biopsy should be carried out before treating an acute rejection episode unless this will substantially delay treatment or pose a significant risk to the patient. Two cores of renal tissue should be obtained at transplant biopsy since this will increase the sensitivity of the investigation. Routine C4d and SV40 staining should be performed upon transplant biopsies to address other causes of graft dysfunction. Look for human leucocyte antigen (HLA)-specific antibodies in serum at the time of renal biopsy.
Treatment of acute rejection: High dose intravenous corticosteroids should be the first line treatment for acute cellular rejection. Maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection. Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III). Antibody mediated rejection (AMR) should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib. After an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximised (2D)
5. Kidney Transplant Recipient:
Chronic Allograft Injury:
Early identification of graft injury is desirable to maximise the potential for intervention.
Renal function should be monitored at each clinic visit by assessment of serum creatinine and qualitative evaluation of urine protein excretion by dipstick, supplemented by spot protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR)
Renal biopsy is the optimal investigation for parenchymal causes of graft dysfunction where the cause is uncertain
Renal biopsies in patients with chronically deteriorating function should be stained for C4d and SV40
Serum sample should be sent at the time of renal biopsy (for graft dysfunction) to look for HLAspecific antibodies.
Chronic allograft injury should be treated:
-By withdrawal of calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy
-By intensification of immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection)
6. Kidney Transplant Recipient: Cardiovascular Disease and Lifestyle
Hypertension
Clinic blood pressure should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
Inhibitors of the renin-angiotensin system may be more effective in the minimisation of proteinuria but should be used with caution in the first 3 months post-transplantResistant hypertension may be due to transplant renal artery stenosis and should be investigated according to local practice
Dyslipidaemia
The choice and dose of statin should take into account concurrent immunosuppression. High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/calcium channel antagonists Diabetes mellitus
The diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting
or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing
A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression
Ischaemic heart disease
We suggest that KTRs receive standard treatment for ischaemic heart disease, including thrombolysis, revascularisation, and secondary prevention
Smoking cessation
Smoking should be strongly discouraged in transplant recipient
Lifestyle measures
Maintenance of a healthy diet should be encouraged
An ideal weight should be targeted (body mass index (BMI) ≤25 kg/m2)
Weight management services should be available
Screening of cancer, Vaccination and treatment of infection.
Level of evidence 5
Clinic infrastructure:
Clinic frequency
Patient Access
Chronic transplant care review
Recognising non-adherence
Immunosuppression regimen
Induction immunosuppression
KTR: Maintenance immunosuppression
Prescribing and the use of generic agents
Diagnosis of acute rejection
Treatment of acute rejection
Diagnosis of Chronic Allograft Injury
Detection of Chronic Allograft Injury
Diagnosis of Chronic Allograft Injury
Treatment of chronic allograft injury
Renal biopsy in chronic allograft injury
Hypertension
Dyslipidemia
Diabetes mellitus
Ischaemic heart disease
Smoking cessation
Lifestyle measures
Screening for cancer
Non-melanoma skin cancer
Immunosuppression in cancers
Vaccination
Prophylaxis and treatment of CMV disease
EBV infection
VZV infection
HSV infection
BK nephropathy
Pneumocystis jirovecii infection – treatment and prophylaxis
Post-transplant infection prophylaxis
Hepatitis E Virus
Osteoporosis
Tertiary hyperparathyroidism
Treatment of gout
Calcineurin inhibitor bone pain
Anaemia
Polycythaemia
Conception and contraception
Conception and contraception (male)
Sexual dysfunction
Level of Evidence:
Level 1 (clinical practice guidelines).
These guidelines are an umbrella document for management of kidney transplant patients starting from developing an infrastructure till close monitoring of these patients covering both clinical and non clinical aspects of management.These guidelines are developed for Non experts but found them useful for any transplant program which wants to provide a standard of care to these patients.
The guidelines cover the areas like
Transplant clinic Logestics
Follow up visits schedule like frequently intially
Immunosupression protocols and how to follow them and intervention when needed
Check of adherence
Post transplant immunization and screening
life style modification and management of HTN , DM and dyslipidemia and ischemic heart disease
Post transplant prophylaxis like CMV , PCP and diagnosing BKVAN early and intervening accordingly
Reproductive issues after transplant
It’s basically a complete document and all transplant programs should follow this in true letter and spirit to provide best possible care to their patients
Post-Operative Care in the Kidney Transplant Recipient
Introduction
· This document is for nonexpert workers in the care of kidney transplant recipients
· The following guidelines meant with healthcare professionals, medical and surgical trainees, general practitioners, nurse specialists, all who deal with kidney transplant patients
· The management of KTR can be divided into two phases:
a. an early post-operative phase when prevention of acute rejection, optimization of graft function and prevention of opportunistic infection are paramount
b. a later phase when the aims are to preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression – malignancy, infection and premature cardiovascular disease.
Summary of Clinical Practice Guidelines for the Post-Operative Care of the Kidney Transplant Recipient
1.Kidney Transplant Recipient (KTR): Organisation of Outpatient Follow-up
KTR: Clinic infrastructure
· Every transplant clinic should be covered by consultant
· KTRs should be reviewed in a dedicated outpatient area
· The results of blood tests should be available within 24 hours
· There should be access to a multidisciplinary renal team including pharmacist, dietician, social worker and psychologist
KTR: Clinic frequency
uncomplicated patients may be reviewed progressively less frequently (2C)
· 2-3 times weekly for the first month after transplantation
· 1-2 times weekly for months 2-3
· Every 2-4 weeks for months 4-6
· Every 4-6 weeks for months 6-12
· 3-6 monthly thereafter
KTR: Patient access
all patients should have access to support services and results. (2C)
KTR: Chronic transplant care review
a detailed review should be performed annually post-operatively (2C)
2. Kidney Transplant Recipient: Non-adherence
KTR: Recognising non-adherence
it is important to prevent and detect non-adherence in kidney transplant recipients. (2C)
3. Kidney Transplant Recipient: Immunosuppressive treatment
the patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression (1D)
KTR: Induction immunosuppression
· Immunosuppressive drugs should be started before or at the time of renal transplantation (1B)
· Induction therapy with biological agents should be administered to all KTRs.
1)an interleukin-2 receptor antagonist (IL2-RA) for patients with low immunological risk .
2) T-cell (lymphocyte) depleting antibodies (TDAs) for higher immunological risk
· Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance (1C)
KTR: Induction immunosuppression
· a CNI should be started at the time of transplantation and not delayed until the graft is functioning (2C)
KTR: Maintenance immunosuppression
· should normally consist of a CNI and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs (1B)
· tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice in patients also taking steroids who are low and medium immunological risk and are not at high risk of developing post transplant diabetes mellitus (PTDM) (2C)
· mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B
· slow release tacrolimus may be used as an option as second line agents for patients who suffer intolerable side effects related to peak dose toxicity (2C)
· the use of second line agents such as ciclosporin, sirolimus, everolimus, or belatacept, if tacrolimus was not tolerated
· MPA-based drugs should be the first-line antiproliferative agent, in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B)
· MMF and enteric-coated mycophenolate sodium provide equivalent maintenance immunosuppression (2B)
· steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients (2B)
· minimum target levels for CNIs in uncomplicated renal transplantation after 3 months
· CNIs should not be withdrawn (2B)
· t if steroids are not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less) (2C)
KTR: Monitoring of immunosuppression
· Tacrolimus and ciclosporin levels should be monitored three times a week initially
· Levels should also be checked if: 1) new drug given 2) the dosage or formulation is changed
3) unexplained graft dysfunction
· Tacrolimus and ciclosporin levels should be available within 24 hours of taking blood samples in the first three months after transplantation
· Sirolimus should be monitored by the C0 trough level
4. Kidney Transplant Recipient: Acute rejection
KTR: Diagnosis of acute rejection
· a transplant renal biopsy should be done before treating an acute rejection episode unless this will delay treatment or pose a significant risk to the patient
· two cores of renal tissue should be obtained at transplant biopsy
· a 16-gauge automated core biopsy needle is suggested to be used
· a protocol transplant renal biopsy is recommended for persisting delayed graft function
· routine C4d and SV40 staining should be performed upon transplant biopsies to address other causes of graft dysfunction
· a serum sample to be sent at the time of renal biopsy (for graft dysfunction) to look for HLA-specific antibodies
KTR: Treatment of acute rejection
· high dose intravenous corticosteroids should be the first line treatment for acute cellular rejection
· maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type
· Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e., Banff category 4 Type II and III)
· AMR should be treated with one or more of the following modalities: steroids; plasma exchange; IVIG; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib
· after an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximized
5. Kidney Transplant Recipient: Chronic Allograft Injury
· renal biopsies in patients with chronically deteriorating function should be stained for C4d and SV40
KTR: Treatment of chronic allograft injury
· By withdrawal of calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy
· By intensification of immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection)
· In a similar fashion to other patients with chronic kidney disease (CKD), following similar preventative strategies and with timely referral to low clearance services
KTR: Renal biopsy in chronic allograft injury. Indicated if:
· a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection
· Every 7-10 days during delayed graft function (DGF)
· If expected renal function is not achieved within 4-8 weeks
· If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol)
6. Kidney Transplant Recipient: Cardiovascular Disease and Lifestyle
KTR: Hypertension
· Blood pressure should be recorded at each clinic visit and should be <140/90 mmHg in clinic
· There is no evidence that any antihypertensive agent is better than any other
· RAS Inhibitors may be more effective in treatment of proteinuria
· Resistant hypertension may be due to transplant renal artery stenosis and should be investigated
KTR: Dyslipidaemia
· Fasting lipid levels should be measured on an annual basis and treat as in the general population
· KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease
· High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/calcium channel antagonists
KTR: Diabetes mellitus
· Screening for post-transplant DM (PTDM) by dipstick urinalysis and measurement of blood sugar level at each clinic visit
· Consider WHO criteria for the diagnosis of DM based on fasting or random blood, serum HBA1c or OGTT
· A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression and should be managed in collaboration with Diabetologist.
· KTR with diabetes should undergo screening for diabetic complications
KTR: Ischaemic heart disease
· KTRs can receive standard treatment for ischaemic heart disease, including thrombolysis, revascularisation, and secondary prevention
· smoking should be strongly discouraged in transplant recipients
KTR: Lifestyle measures
· a healthy diet and body mass index (BMI) ≤25 kg/m2
· Limited alcohol consumption and avoidance recreational drug use
· Discourage the use of over-the-counter medications and herbal medicines.
7. Kidney Transplant Recipient: Neoplasia
· Screening should be similar to the general population for cervical, breast, colon and prostate cancer and not recommended for renal cell carcinoma
· Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant
· Patients with cirrhosis should undergo an annual hepatic ultrasound and determination of serum alpha fetoprotein
· KTRs should be educated about the adverse effects of sun exposure and to cover their skin in direct sunlight and to use total sunbloc
· self-examination should be encouraged with guidance provided, at least biannual review by a up to 5 years post-transplant and annual review from 5 years
· Consider acitretin as chemoprophylaxis for those with ≥2 previous Non-melanoma skin cancer if there are no contraindications
· immunosuppression should be reduced if neoplasia develops and consider m-TORi as alternative immunosuppressive agent
· m-TORs have specific anti-tumor effects in Kaposi sarcoma
Kidney Transplant Recipient: Infection Complications
KTR: Vaccination
· KTRs Should be vaccinated with inactivated viruses as per the normal population and receive annual influenza vaccination unless contraindicated
· KTRs Should have HBsAb levels rechecked annually and be revaccinated if antibody titres fall below 10 mIU/mL
· KTRs Should not receive live attenuated vaccines
· KTRs Should receive pneumococcal vaccine and a booster every five years
KTR: Cytomegalovirus (CMV) disease
· Prophylaxis should be continued for 3-6 months, until immunosuppression has been reduced to long-term maintenance level
· Treatment should be administered for 6 weeks after treatment with a TDA
· For the treatment of mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are of equivalent efficacy
· The first line treatment of life-threatening CMV disease is intravenous ganciclovir with monitoring viral load to assess duration of treatment
KTR: Epstein Barr Virus (EBV) infection
· immunosuppression should be reduced or stopped following the development of post- transplant lymphoproliferative disease (PTLD)
· All high risk (D+ /R-) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year
· EBV viral load should be monitored after the treatment of rejection, with reduction of immunosuppression when EBV titres rise significantly
KTR: Varicella Zoster Virus (VZV) infection
· Primary infection (chickenpox) should be treated with IV aciclovir or oral valaciclovir until the lesions scab over
· Uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over
· Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with IV aciclovir until the lesions scab over, together with a reduction in immunosuppression
· Varicella-susceptible KTRs (i.e. VZV IgG negative) with primary exposure to VZV should receive IVIG, ideally within 96 hours, but up to a maximum of 10 days following exposure. If unavailable or after 10 days, oral aciclovir should be prescribed for seven days
· Patients on the waiting list who are VZV IgG negative should be vaccinated prior to transplantation, and Immunosuppression should be reduced during primary infection
KTR: Herpes Simplex Virus (HSV) infection
· KTRs suffering frequent recurrent HSV infection should consider oral prophylaxis
KTR: BK virus (BKV) nephropathy
· confirmed BK nephropathy should be treated by reduction in immunosuppression (no specific treatment)
· KTRs should be screened for BKV viral load or by performing urine microscopy for decoy cells or by PCR on urine or serum
· Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40
· Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml
· Re-transplantation can safely be considered in patients who have BK nephropathy diagnosed in an earlier graft
KTR: Pneumocystis jirovecii infection – treatment and prophylaxis
· All patients with Pneumocystis jirovecii should be treated for 14 to 21 days with co-trimoxazole orally or intravenously (15-20mg/kg in three or four divided doses)
· Patients with contraindications to treatment with co-trimoxazole should receive pentamidine (4mg/kg/day intravenously)
· Adjunctive glucocorticoid therapy may be considered in patients with severe disease
· All patients should receive 3-6 months of treatment with co-trimoxazole 480mg daily for Pneumocystis jirovecii prophylaxis following renal transplantation
KTR: Hepatitis E Virus (HEV)
Hepatitis E Virus (HEV)-screened blood components should be given to all KTR
Kidney Transplant Recipient: Bone and Joint Disease
KTR: Osteoporosis
· KTRs suffering from osteoporosis or at high potential risk should be considered for steroid-avoiding immunosuppression
· KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2
· Treatment should be according to the Royal College of Physicians (RCP) guidelines for steroid-induced osteoporosis
KTR: Tertiary hyperparathyroidism
· Severe hyperparathyroidism should be treated prior to transplantation
· Cinacalcet can be used in KTR
· Treatment should be the same as for other patients with CKD
KTR: Gout
· neither allopurinol nor febuxostat should be administered with azathioprine
· Hyperuricaemia should be treated when associated with gout, tophi or uric acid stones
· NSAIDs should be avoided in KTRs
· Acute gout may be treated with brief a course of oral prednisolone, and Colchicine is an effective treatment for gout in KTR
KTR: Calcineurin inhibitor bone pain
· Reduction or withdrawal of CNIs should be considered in KTRs with intractable bone pain
· Dihydropyridine calcium antagonists also may be beneficial
Kidney Transplant Recipient (KTR): Haematological Complications
· chronic anaemia should be managed in the same way as other patients with CKD
· Polycythaemia initial treatment should be with ACEIs or ARBs, if the haematocrit or exceeds 52% in men and 49% in women
· Venesection may be used in refractory Polycythaemia cases
Kidney Transplant Recipient (KTR): Reproductive Issues
· MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately
· KTRs should wait for one year after transplant and have stable function before attempting conception
· m-TORi should be stopped prior to conception and replaced as appropriate
· KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth of the baby unless there are contraindications
· The risks and benefits of breastfeeding should be discussed
· Contraception advice should be similar to the general population
· Male KTRs are advised that MPA containing compounds have theoretical teratogenic potential in men taking these agents
· KTRs should be advised that m-TORi reduce the male sperm count and counselled accordingly
· All immunosuppressive drugs other than m-TORi can be used in male KTRs
· The decision to continue MPA containing compounds in a male KTR wishing to conceive should balance the risk of theoretical teratogenicity against the risk of rejection on changing from MPA to azathioprine
· Men on m-TORi who wish to conceive should discontinue these agents prior to conception and replace them as appropriate
· Men who wish to maintain fertility should avoid m-TORi or bank sperm prior to starting these drugs
· For sexual dysfunction Sildenafil is safe and effective in male KTR not taking nitrates
This is Editorials evidence 5
Summary of the article
“Post-Operative Care in the Kidney Transplant Recipient (BTS GUIDELINES- 2017)”
KTR: Clinic frequency
We suggest that uncomplicated patients may be reviewed progressively less frequently (2C)
· 2-3 times weekly for the first month after transplantation
· 1-2 times weekly for months 2-3
· Every 2-4 weeks for months 4-6
· Every 4-6 weeks for months 6-12
· 3-6 monthly thereafter
KTR: immunosuppression regimen
We recommend that the patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression (1D)
KTR: Induction immunosuppression
We recommend induction therapy should take into account the following:
· Immunosuppressive drugs should be started before or at the time of renal transplantation (1B)
· Induction therapy with biological agents should be administered to all KTRs. In patients at low immunological risk this will generally involve an interleukin-2 receptor antagonist (IL2-RA). Recipients at higher immunological risk may be considered for T-cell (lymphocyte) depleting antibodies (TDAs)(1B)
· Induction therapy with TDAs may also be useful for lower immunological risk patients with the intention of either steroid or calcineurin inhibitor (CNI) avoidance (1C)
KTR: Induction immunosuppression
· We suggest that a CNI should be started at the time of transplantation and not delayed until the graft is functioning (2C) .
KTR: Maintenance immunosuppression
· We recommend that maintenance immunosuppression should normally consist of a calcineurin inhibitor (CNI) and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs (1B).
· We suggest that low-medium dose tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice in patients also taking steroids who are low and medium immunological risk and are not at high risk of developing post transplant diabetes mellitus (PTDM) (2C).
· We suggest that mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B).
· We suggest that slow release tacrolimus may be used as an option as second line agents for patients who suffer intolerable side effects related to peak dose toxicity (2C).
· We suggest that KTRs who are unable to tolerate tacrolimus or who suffer serious adverse reactions related to its use be considered for the use of second line agents such as ciclosporin, sirolimus, everolimus, or belatacept (1B)
· We suggest that MPA-based drugs should be the first-line antiproliferative agent, in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception (2B).
· We suggest that mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (Myfortic®) provide equivalent maintenance immunosuppression (2B)
· We suggest that steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients (2B)
· We suggest aiming for minimum target levels for CNIs in uncomplicated renal transplantation after 3 months (2C)
· We suggest that CNIs should not be withdrawn (2B)
· We suggest that if steroids are not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less) (2C)
KTR: Monitoring of immunosuppression
We suggest that long-term monitoring of immunosuppression levels is required as follows:
· Tacrolimus and ciclosporin levels should be monitored. The initial frequency should be three times a week. Levels should also be checked when any medication with possible interactions is prescribed, the dosage is changed, the formulation is changed, or when there is unexplained graft dysfunction (2C)
· Tacrolimus should be monitored by the trough (C0) level, while ciclosporin can be monitored by either C0 or 2- hour post dose (C2) level (2C)
· Tacrolimus and ciclosporin levels should be available within 24 hours of taking blood samples in the first three months after transplantation (2D)
· The utility of monitoring mycophenolic acid (MPA) C0 levels is uncertain (2D)
· Sirolimus should be monitored by the C0 trough level (2C)
KTR: Prescribing and the use of generic agents
· We suggest that generic immunosuppression compounds should not be used unless they have been shown to be bioequivalent and approved by the European Agency for the Evaluation of Medicinal Products (2D).
· We suggest that KTRs should be made aware of the existence of generics and the importance of not switching between preparations without appropriate supervision (2D)
· We suggest that drugs should be prescribed by brand name (whether branded or generic drugs are prescribed) (2D)
· We suggest that KTRs should be closely monitored after switching between generic preparations until a new steady state is established (2D)
KTR:Acute rejection
a) Diagnosis of acute rejection
· We recommend that a transplant renal biopsy should be carried out before treating an acute rejection episode unless this will substantially delay treatment or pose a significant risk to the patient (1C)
· We recommend that a transplant renal biopsy should be carried out before treating an acute rejection episode unless this will substantially delay treatment or pose a significant risk to the patient (1C)
· We suggest that two cores of renal tissue should be obtained at transplant biopsy since this will increase the sensitivity of the investigation (2C)
· We suggest that a 16 gauge automated core biopsy needle is used where possible to provide the best compromise between diagnostic usefulness and patient tolerance of the procedure (1C)
· We recommend that a protocol transplant renal biopsy, defined as a biopsy performed in a stable graft without clinical evidence of acute rejection, be considered in the setting of persisting delayed graft function (1C)
· We recommend that routine C4d and SV40 staining should be performed upon transplant biopsies to address other causes of graft dysfunction (2C)
· We suggest that a serum sample be sent at the time of renal biopsy (for graft dysfunction) to look for human leucocyte antigen (HLA)-specific antibodies (2C)
b) KTR: Treatment of acute rejection
· We suggest that borderline acute cellular rejection should be treated in the context of acute graft dysfunction (2D)
· We recommend that high dose intravenous corticosteroids should be the first line treatment for acute cellular rejection (1D)
· We suggest that maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type (2D)
· We suggest that lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III) (2C)
· We suggest that antibody mediated rejection (AMR) should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib (2C)
· We recommend that the British Transplant Society (BTS) guidelines on antibody incompatible transplantation for management of rejection in the context of antibody incompatible transplantation (1A-D)
· We suggest that – after an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, MPA should be started, or the existing dose of MPA maximised (2D)
KTR: Chronic Allograft Injury
a) KTR:Diagnosis of Chronic Allograft Injury
· We recommend that early identification of graft injury is desirable to maximise the potential for intervention. A proactive and systematic approach should employed to manage graft dysfunction (1C)
· We suggest that renal function should be monitored at each clinic visit by assessment of serum creatinine and qualitative evaluation of urine protein excretion by dipstick, supplemented by spot protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR) if positive (2C)
· We suggest that renal biopsy is the optimal investigation for parenchymal causes of graft dysfunction where the cause is uncertain (2C)
· We suggest that renal biopsies in patients with chronically deteriorating function should be stained for C4d and SV40 (2C)
· We suggest that a serum sample should be sent at the time of renal biopsy (for graft dysfunction) to look for HLA- specific antibodies (2C)
b) KTR: Treatment of chronic allograft injury
We suggest that chronic allograft injury should be treated:
· By withdrawal of calcineurin inhibitors if there is histological evidence of CNI toxicity or non-specific interstitial fibrosis and tubular atrophy (2C)
· By intensification of immunosuppression if there is evidence of ongoing immune injury (cellular rejection and/or humoral rejection) (2C)
· In a similar fashion to other patients with chronic kidney disease (CKD), following similar preventative strategies and with timely referral to low clearance services (2D)
c) KTR: Renal biopsy in chronic allograft injury
We suggest that a renal transplant biopsy is indicated:
· If there is a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection (BPAR) (1C)
· Every 7-10 days during delayed graft function (DGF) (2C)
· If expected renal function is not achieved within 4-8 weeks (2D)
· If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol) (2C)
KTR:Cardiovascular Disease and Life style
a) KTR: Hypertension
We suggest that the management of hypertension take into account that:
· Blood pressure should be recorded at each clinic visit (1C)
· Clinic blood pressure should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
· Home blood pressure recordings and 24-hour ambulatory recordings may be helpful in some instances but lower BP targets should then be set (home and or ambulatory daytime measures <135/80mmHg) (2D)
· There is no evidence that any antihypertensive agent is better than any other and effort should be focused on achieving absolute blood pressure control rather than the use of individual agents (2D)
· Inhibitors of the renin-angiotensin system may be more effective in the minimisation of proteinuria but should be used with caution in the first 3 months post-transplant.(2C)
· Resistant hypertension may be due to transplant renal artery stenosis and should be investigated according to local practice (2D)
b) KTR: Dyslipidaemia
We suggest that the management of dyslipidaemia take into account that:
· Fasting lipid levels should be measured on an annual basis in renal transplant recipients (2C)
· Treatment targets should be the same as in the general population (2C)
· KTRs at increased primary or secondary cardiovascular risk receive statin therapy to reduce the risk of coronary artery disease (2C)
· The choice and dose of statin should take into account concurrent immunosuppression. High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/calcium channel antagonists (2D)
c) KTR: Diabetes mellitus
We suggest that the detection and treatment of diabetes should consider:
· Screening for the development of post-transplant diabetes mellitus (PTDM) by dipstick urinalysis and measurement of blood sugar level at each clinic visit (2C)
· Post-transplant immunosuppression should take into account risk factors for the development of diabetes (2C)
· The diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing (1C)
· A diagnosis of PTDM is made once patients are established on stable maintenance immunosuppression (2D)
· Post-transplant diabetes should be managed in collaboration with specialists in diabetic medicine (2D)
· All units should have a protocol for the management of post-transplant diabetes (2C)
· KTR with diabetes (either prior to transplantation or PTDM) should undergo screening for diabetic complications (retinal screening, foot care, neuropathy) in line with guidelines for non KTR patients with diabetes (2D)
d) KTR: Ischaemic heart disease
· We suggest that KTRs receive standard treatment for ischaemic heart disease, including thrombolysis, revascularisation, and secondary prevention (2C)
e) KTR: Smoking cessation
· We recommend that smoking should be strongly discouraged in transplant recipients (see guideline 6.4) (1A)
f) KTR: Lifestyle measures
We suggest that advice on healthy lifestyle forms a routine part of post-transplant care:
· Maintenance of a healthy diet should be encouraged (2C)
· An ideal weight should be targeted (body mass index (BMI) ≤25 kg/m2) (2C)
· Weight management services should be available (2C)
· We suggest that KTRs participate in physical activity at a level similar to that recommended to age and comorbidity matched counterparts from the general population (2D)
· Alcohol consumption should be within national guidelines (2D)
· Recreational drug use should be avoided (2D)
· The use of over-the-counter medications (without discussion with clinical staff) and non-proprietary medications (e.g. herbal medicines) should be discouraged (2D)
KTR:Neoplasia
a) KTR: Screening for cancer
We suggest that the organisation of screening for neoplasia in KTRs take into account:
· Screening should be similar to the general population for cervical, breast, colon and prostate cancer (2C)
· Screening is not recommended for renal cell carcinoma (2C)
· Patient education pre and post transplantation (1C)
· Patients should be aware of malignancy risk and encouraged to report symptoms which may represent de novo malignancy (e.g. breast or testicular lumps) (2D)
· Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant (2C)
· Patients with cirrhosis should undergo an annual hepatic ultrasound and determination of serum alpha fetoprotein (2C)
b) KTR: Non-melanoma skin cancer (NMSC)
· We recommend that KTRs should be educated about the adverse effects of sun exposure (1C)
c) KTR: Non-melanoma skin cancer
· We suggest that KTRs that an individualised assessment of hazard should be made according to risk factors (2C)
· We recommend that patients should be encouraged to cover their skin in direct sunlight and to use total sunblock (Sun Protection Factor ≥50) (1D)
· We suggest that self-examination should be encouraged with guidance provided. This should be supplemented by at least biannual review by a trained healthcare professional up to 5 years post-transplant and annual review from 5 years (2C)
· We suggest that the prescription of acitretin as chemoprophylaxis be considered in those with ≥2 previous NMSC if there are no contraindications (2B)
KTR: Immunosuppression in cancers
· We suggest that immunosuppression should be reduced if neoplasia develops (2C)
· We suggest that mammalian target of rapamycin inhibitors (m-TORi) are considered as alternative immunosuppressive agents in KTRs who develop de novo malignancy (2C)
· Kaposi sarcoma: We suggest that m-TORs have specific anti-tumour effects in Kaposi sarcoma (2C)
KTR:Infection Complications
a) Vaccination;We recommend that KTRs:
· Should be vaccinated with inactivated viruses as per the normal population (1D)
· Should receive annual influenza vaccination unless contraindicated (1C)
· Should have hepatitis B surface antibody (HBsAb) levels rechecked annually and be revaccinated if antibody titres fall below 10 mIU/mL (2D)
· Should not receive live attenuated vaccines (2C)
· Should receive pneumococcal vaccine and a booster every five years (2D)
b) KTR: Cytomegalovirus (CMV) disease
Prophylaxis and treatment of CMV disease, we recommend:
· Prophylaxis should be continued for 3-6 months, until immunosuppression has been reduced to long-term maintenance level (1B)
· Treatment should be administered for 6 weeks after treatment with a TDA (1C)
· All transplant units should be able to measure CMV serological status and quantify viral load (2D)
· Donor and recipient CMV status should be recorded at the time of transplantation (2D)
· Each unit should have a written protocolised CMV strategy based on prophylaxis or pre-emptive therapy (2D)
· For the treatment of mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are of equivalent efficacy (2C)
· The first line treatment of life-threatening CMV disease is intravenous ganciclovir (2D)
· Treatment duration should be determined by monitoring viral load (2C)
c) KTR: Epstein Barr Virus (EBV) infection
· We recommend that immunosuppression should be reduced or stopped following the development of post transplant lymphoproliferative disease (PTLD) (1C)
· We suggest:
a. Both donor and recipient should have their EBV serology recorded at the time of transplantation (2D)
b. All high risk (D+/R-) patients (including adults) should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year (2C)
c. EBV viral load should be monitored after the treatment of rejection (2C)
d. Total immunosuppression should be reduced when EBV titres rise significantly (2C)
d) KTR: Varicella Zoster Virus (VZV) infection
We recommend:
· Primary infection (chickenpox) should be treated with intravenous aciclovir or oral valaciclovir until the lesions scab over (1C)
· Uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over (1D)
· Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with intravenous aciclovir until the lesions scab over, together with a reduction in immunosuppression (1B)
· Varicella-susceptible KTRs (i.e. VZV IgG negative) with primary exposure to VZV should receive intravenous immunoglobulin, ideally within 96 hours, but up to a maximum of 10 days following exposure. If unavailable or after 10 days, oral aciclovir should be prescribed for seven days (1D)
· We suggest:
a. Patients on the waiting list who are VZV IgG negative should be vaccinated prior to transplantation (2D)
b. Immunosuppression should be reduced during primary infection (2D)
e) KTR: Herpes Simplex Virus (HSV) infection
We recommend:
· Superficial HSV infection should be treated with appropriate oral agents until the lesions have resolved (1D)
· Systemic HSV infections should be treated with intravenous aciclovir and a reduction in immunosuppression until a response occurs and oral medication should be continued for at least 14 days (1C)
· We suggest that KTRs suffering frequent recurrent HSV infection should consider oral prophylaxis (2D)
f) KTR: BK virus (BKV) nephropathy
· We recommend that confirmed BK nephropathy should be treated by reduction in immunosuppression (1D)
· We suggest:
a. Screening should also be carried out when renal function deteriorates in an unexplained fashion (2D)
b. KTRs should be screened for BKV viral load or by performing urine microscopy for decoy cells or by polymerase chain reaction (PCR) on urine or serum (2C)
c. Suspected BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40. Two cores containing medullary tissue should ideally be examined (2D)
d. Immunosuppression should be reduced when the serum BKV load exceeds 104 copies/ml (2C)
e. There is no established specific treatment for BK nephropathy (2D)
g) KTR: Pneumocystis jirovecii infection – treatment and prophylaxis
We suggest:
· All patients with confirmation (microscopy or PCR) of Pneumocystis jirovecii in respiratory secretions should be treated for 14 to 21 days with co-trimoxazole orally or intravenously (15-20mg/kg in three or four divided doses) (2B)
· Patients with contraindications to treatment with co-trimoxazole should receive pentamidine (4mg/kg/day intravenously) (2B)
· Adjunctive glucocorticoid therapy may be considered in patients with severe disease (2D)
· KTR: Pneumocystis jirovecii infection; for post-transplant infection prophylaxis, we suggest:
a. All patients should receive 3-6 months of treatment with co-trimoxazole 480 mg daily (1B)
b. Oral antifungal prophylaxis should be administered for one week after transplantation (2C)
c. In selected patients, prophylaxis against mycobacterium tuberculosis with daily isoniazid (supplemented with pyridoxine) should be instituted for six months after transplantation (2C)
h) KTR: Hepatitis E Virus (HEV)
· We recommend that Hepatitis E Virus (HEV)-screened blood components should be given to all KTR (1C)
KTR:Bone and JointDisease
a. KTR: Osteoporosis; We suggest:
· KTRs suffering from osteoporosis or at high potential risk should be considered for steroid-avoiding immunosuppression (2D)
· KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2 (2D)
· Treatment should be according to the Royal College of Physicians (RCP) guidelines for steroid-induced osteoporosis (2D)
b. KTR: Tertiary hyperparathyroidism
· Severe hyperparathyroidism should be treated prior to transplantation (2D)
· Cinacalcet can be used in KTR (2C)
· Treatment should be the same as for other patients with CKD (2D)
c. KTR: Gout
· We recommend that neither allopurinol nor febuxostat should be administered with azathioprine (1C)
· We suggest:
a. Hyperuricaemia should be treated when associated with gout, tophi or uric acid stones (2D)
b. Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided in KTRs (2D)
c. Acute gout may be treated with brief a course of oral prednisolone. (2D)
d. Colchicine is an effective treatment for gout in KTR (2D)
d. KTR: Calcineurin inhibitor bone pain
We suggest:
· Reduction or withdrawal of CNIs should be considered in KTRs with intractable bone pain (2D)
· Dihydropyridine calcium antagonists also may be beneficial (2D)
KTR: Haematological Complications
a) Anaemia
· We suggest that chronic anaemia should be managed in the same way as other patients with CKD (2D)
b) polycythemia
· We recommend that initial treatment should be with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) (1C)
· We suggest:
a. Haemoglobin levels should be monitored at every clinic visit (2D)
b. Treatment should be initiated if the haematocrit or packed cell volume exceeds 52% in men and 49% in women (2D)
c. Venesection may be used in refractory cases.(2D)
KTR: Reproductive Issues
a) KTR: Conception and contraception (female) KTR:
· We recommend that MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately (1A)
· We suggest:
a. KTRs should wait for one year after transplant and have stable function before attempting conception (2C)
b. Counselling regarding fertility and reproduction should be offered to female KTRs and their partners either prior to transplantation or soon afterwards (2D)
c. m-TORi should be stopped prior to conception and replaced as appropriate (2D)
d. Pregnancy should be jointly managed with an Obstetrics department with experience of care of KTR (2D)
e. KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth of the baby unless there are contraindications (2C)
f. The risks and benefits of breastfeeding should be discussed (2D)
g. Contraception advice should be similar to the general population (2D)
b) Conception and contraception (male)
We recommend:
· Male KTRs are advised that MPA containing compounds have theoretical teratogenic potential in men taking these agents (1D)
· KTRs should be advised that m-TORi reduce the male sperm count and counselled accordingly. (1C)
· We suggest:
a. All immunosuppressive drugs other than m-TORi can be used in male KTRs. Advice for MPA is as Guideline 11.3 (2D)
b. The decision to continue MPA containing compounds in a male KTR wishing to conceive should balance the risk of theoretical teratogenicity against the risk of rejection on changing from MPA to azathioprine (2D)
c. Men on m-TORi who wish to conceive should discontinue these agents prior to conception and replace them as appropriate (2D)
d. Men who wish to maintain fertility should avoid m-TORi or bank sperm prior to starting these drugs (2D)
c) KTR: Sexual dysfunction
We suggest:
· Specific enquiry should be made regarding sexual dysfunction, preferably at an annual review clinic (2D)
· Care pathways for dealing with sexual dysfunction should be established (2D)
· Close liaison with local andrology service is recommended (2D)
· Sildenafil is safe and effective in male KTR not taking nitrates (2D)
What is the evidence provided by this article?
This is a clinical practice guidelines.
Level of evidence grade 1.
Clinical Practice Guidelines for the Post-Operative Care of the Kidney Transplant Recipient.
Final Version February 2017
Review Date February 2022
1-Clinic infrastructure.
The place dedicated for transplant recipient follow up, should be in outpatient area with consultant-level health care professional supervision, blood test results should be available and reviewed within 24 hours .
2-Clinic frequency.
uncomplicated patients may be reviewed progressively less frequently
2-3 times weekly for the first month after transplantation.
1-2 times weekly for months 2-3.
Every 2-4 weeks for months 4-6.
Every 4-6 weeks for months 6-12.
3-6 monthly thereafter.
3-Patient access.
All patients should have access for their labs results, access for inquires and information should be available in both written and electronic formats.
4-Recognising non-adherence.
Should prevent and detect non-adherence in kidney transplant recipients by determine factors of non-adherence and should establish Pathways should be in place for pediatric KTRs in transition and for adolescent KTRs.
5-immunosuppression regimen.
Our plan should be discussed with the recipient and decisions around selection of induction agent and maintenance immunosuppression.
A-Induction therapy.
Should be started before or at the time of renal transplantation and interleukin-2 receptor antagonist (IL2-RA) for lower immunological risk and T-cell (lymphocyte) depleting antibodies for higher immunological risks and can be used also with lower immunological risks with the intention of
either steroid or calcineurin inhibitor (CNI) avoidance, not to delay CNIs till graft become functioning .
B-Maintenance immunosuppression.
=For patients who are low and medium immunological risk and are not at high risk of developing post transplant diabetes mellitus (PTDM) start tacrolimus with low trough level 4-8, mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception.
=Pt who complain of side effects related to tacrolimus peak dose toxicity, the slow release tacrolimus is indicated.
=Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients.
Monitoring of immunosuppression.
We should monitor tacrolimus, cyclosporine and sirolimus by before the dose or after the dose as in cyclosporine C2, and should be available within 24 hours in the first 3 months.
Acute rejection.
=16 gauge automated core biopsy needle used to bring 2 cores and biopsy better to be done before treatment unless there is a significant risk to the patient.
=We recommend that a protocol transplant renal biopsy be considered in the setting of persisting delayed graft function.
=We recommend that routine C4d and SV40 staining and send blood sample for (HLA)-specific antibodies.
Treatment of acute rejection.
=High dose intravenous corticosteroids should be the first line treatment for acute cellular rejection and treatment of borderline rejection, maintenance steroids should be added or restarted in steroid-free patients.
=For refractory acute cellular rejection or aggressive vascular cellular rejection, lymphocyte depleting agents might be considered.
=Antibody mediated rejection (AMR) should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or Bortezomib.
Chronic Allograft Injury.
=To diagnose CAI , we should serially follow up serum creatinine and urine PCR , and if suspected, renal biopsy should be done and be stained for C4d and SV40, and send blood sample for HLA specific antibodies.
=If there is signs of immune injuries , intensification of immunosuppression is required .
=If there are signs of chronic CNI toxicity , withdrawal is recommended.
Renal biopsy in chronic allograft injury.
If there is a persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection (BPAR) .
Every 7-10 days during delayed graft function (DGF) (2C)
If expected renal function is not achieved within 4-8 weeks (2D)
If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol).
KTR: Hypertension.
-Strict F/U of BP and home measurement suggested and to keep target less than 140/90 mmHg and no specific type of anti-HTN medication preferred over the others .
-We should suspect RAS with resistant HTN specially in the first 3 months.
KTR: Dyslipidemia.
Fasting lipid profile should be followed annually and treated as general population criteria , should keep in mind statin with CNI interaction, for example high dose simvastatin (≥40mg daily) should be avoided in conjunction with cyclosporine and/calcium channel antagonists.
KTR: Diabetes mellitus.
=Screening by dipstick urinalysis and measurement of blood sugar level at each clinic visit, the diagnosis of PTDM is made based on WHO criteria for the diagnosis of diabetes mellitus based on fasting or random blood, serum glycated haemoglobin (HBA1c) or oral glucose tolerance testing .
Screening for diabetic complications (retinal screening, foot care, neuropathy) in line with guidelines for non KTR patients with diabetes .
KTR: Ischaemic heart disease.
We suggest that KTRs receive standard treatment for ischaemic heart disease, including thrombolysis, revascularization, and secondary prevention and smoking should be strongly discouraged.
KTR: Screening for cancer.
-For cervical, breast, colon and prostate cancer, patients should be aware of malignancy risk and encouraged to report symptoms which may represent de novo malignancy (e.g. breast or testicular lumps) and Skin surveillance by a healthcare professional should be done every year, 5years after KTX.
KTR: Non-melanoma skin cancer (NMSC).
=Pt should be educated about side effects of direct exposure to sunlight and importance of sun block use.
=Immunosuppression should be reduced if neoplasia develops .
=Mammalian target of rapamycin inhibitors (m-TORi) are considered as alternative immunosuppressive agents in KTRs who develop de novo malignancy, specially with Kaposi sarcoma.
KTR: Vaccination.
Suggest to give all inactive vaccination as normal population and Should not receive live attenuated vaccines, annual influenza vaccine, pneumococcal vaccine and a booster every five years and f/u HBV s ab annually and booster dose according to titer.
KTR: Cytomegalovirus (CMV) disease.
Prophylaxis should be continued for 3-6 months and Treatment should be administered for 6 weeks after treatment with a TDA.
For the treatment of mild and moderate CMV disease, oral Val ganciclovir or intravenous ganciclovir.
The first line treatment of life-threatening CMV disease is intravenous ganciclovir and treatment duration should be determined by monitoring viral load.
KTR: Epstein Barr Virus (EBV) infection.
Immunosuppression should be reduced or stopped following the development of post transplant lymphoproliferative disease (PTLD).
EBV viral load should be monitored after the treatment of rejection.
KTR: Varicella Zoster Virus (VZV) infection.
Primary infection (chickenpox) should be treated with intravenous acyclovir or oral valaciclovir and uncomplicated shingles should be treated with oral acyclovir or valaciclovir until the lesions scab over and disseminated (>2 dermatomes), ocular or invasive shingles should be treated with intravenous acyclovir with reduction of immunosuppression.
KTRs who is VZV IgG negative and exposed to diseased person should receive intravenous immunoglobulin, ideally within 96 hours, but up to a maximum of 10 days . If unavailable or after 10 days, oral acyclovir should be prescribed for seven days.
KTR: BK virus (BKV) nephropathy.
Immunosuppression should be reduced once diagnosed with serum BKV load exceeds 104 copies/ml, screening is important by serum or urine PCR or urine decoy cell in urine, BK nephropathy should be confirmed by renal biopsy, which should be stained for SV40.
BK nephropathy diagnosed in an earlier graft is considered not contraindication for re-transplant.
KTR: Pneumocystis jirovecii infection – treatment and prophylaxis.
Treated for 14 to 21 days with co-trimoxazole orally or intravenously and if contraindicated pentamidine is used.
KTR: Post-transplant infection prophylaxis.
All patients should receive 3-6 months of treatment with co-trimoxazole 480 mg daily .
Oral antifungal prophylaxis should be administered for one week after transplantation.
KTR: Osteoporosis.
Steroid free protocol for high risk patient and better to undergo DEXA scanning if eGFR >30 mL/min/1.73m.
KTR: Tertiary hyperparathyroidism.
Severe hyperparathyroidism should be treated prior to transplantation and treatment should be the same as for other patients with CKD.
KTR: Gout.
Hyperuricemia associated with gout , tophi or stone should be treated with steroid and or colchicine, NSAID should be avoided and neither allopurinol nor febuxostat should be administered with azathioprine.
KTR: Calcineurin inhibitor bone pain.
Reduction or withdrawal of CNIs should be considered in KTRs with intractable bone pain and dihydropyridine calcium antagonists also may be beneficial.
KTR: Polycythaemia.
ACEI or ARBs is the first line of treatment and venesection can be used in refractory cases.
KTR: Conception and contraception (female).
MPA-containing immunosuppressant drugs & m-TORi should be stopped prior to conception and replaced appropriately.
Counselling both partners about Fertility and reproduction , should be planned with special criteria (stable normal function test for one year post KTX) with MDT follow up.
Aspirin decrease pre-eclampsia incidence , starting from 12 weeks gestation until birth.
KTR: Conception and contraception (male).
All immunosuppressive drugs other than m-TORi can be used in male KTRs because it lead to low sperm count and decision to continue MPA containing compounds in a male KTR wishing to conceive should balance the risk of theoretical teratogenicity against the risk of rejection on changing from MPA to azathioprine.
Men who wish to maintain fertility should avoid m-TORi or bank sperm prior to starting these drugs .
Level of evidence V
Club 7; post operative care in KT
Summary
· Consultant level medical professional must be present in each OPC.
· Follow up lab should be reviewed within 24 h, trough levels of CNI should be adjusted.
· Frequency of follow up: 2-3 times weekly for the first month, then 1-2 times weekly for months 2-3, then every 2-4 weeks for months 4-6, then every 4-6 weeks for months 6-12 and 3-6 monthly thereafter.
· Brand form of drugs should be used, generic immunosuppression compounds should not be used unless they have been shown to be bioequivalent and approved by the European Agency for the Evaluation of Medicinal Products.
· Never shift between formulations without appropriate supervision, and those patients should be closely monitored after switching between generic preparations until a new steady state is established.
· Induction therapy includes anti IL 2 Rc antibodies in case of low immunological risk, and ATG in high immunological risk.
· Maintenance therapy includes CNI, MMF and steroids.
· Azathioprine is used instead of MMF in case of pregnancy, lactation, fertile patient,unwilling to receive MMF.
· CNI is used life long, while steroids can be maintained on very low dose (5 mg/day).
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· Diagnosis of acute rejection should be biopsy based (require 2 cores of renal tissue), without delay in starting treatment.
· Biopsy needed to be graded according to Banff classification.
· Routine staining with C4d and SV40 is needed to exclude other causes of acute graft dysfunction.
· Serum testing for DSA is needed together with biopsy.
· Treatment of acute rejection:
o Borderline acute cellular rejection should be treated
o High dose pulse steroids is 1st line in ttt of acute CMR.
o ATG is used in refractory acute cellular rejection or in vascular injury (Banff Type II and III) .
o Adjustment of maintenance therapy (increase CNI dose to achieve trough level) or restart steroids after its withdrawal or add it in steroid free regimens or shift from azathioprine to MMF or increase dose of MMF.
o ABMR can be treated by any of the following: IVIg; anti-CD20 antibody (rituximab), lymphocyte-depleting antibody (ATG) or bortezomib.
· Follow up of blood pressure and proteinuria (Presence of proteinuria by dipstick, should be quantified by spot ACR or PCR).
· Renal biopsy is the most important tool in case of unidentified cause of graft dysfunction (chronic allograft dysfunction).
· Management of chronic graft dysfunction:
o Decrease CNI (if evidence of toxicity).
o Increase immunosuppression if any evidence of immune mediated graft damage.
o Supportive measures as in CKD patients.
· Control of dyslipidemia and statin used to minimize cardiovascular morbidity and mortality.
· Indications of graft biopsy in chronic allograft injury:
o persistent unexplained elevation of creatinine or failure to return to baseline after an episode of biopsy proven acute rejection.
o (Every 7-10 days during delayed graft function (DGF)
o If expected renal function is not achieved within 4-8 weeks
o Sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol).
· Management of hypertension;
o Measure ABP at office and ambulatory blood pressure measurement may be needed,
o No consensus about best antihypertensive drug, ACEis are preferred due added antiprotinuric effect (However, must be used with caution in the first 3 months post-transplant).
o Renal artery stenosis should be treated to control hypertension.
· Management of dyslipidemia:
o Fasting blood lipid should be measured annually.
o Control of its level as in general population to reduce risk of astherosclerosis.
o Statin is 1st line, however, caution should be taken as high dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/CCB.
· Management of diabetes mellitus:
o Is related to steroids and tacrolimus use.
o Diagnosis according to standards of DM (fasting> 126 mg/dl, post prandial >180 mg/dl, random glucose > 200 mg/dl, HBA1c > 6.5 ).
o Screening of complications (fundus for retinopathy, microalbumin for nephropathy)
· Management of ischemic heart disease:
o Treatment either thrombolytic therapy or revasculaization.
· Vaccination;
o Should be vaccinated upto date.
o Annual influenza vaccine is indicated, and receive pneumococcal vaccine and a booster every five years.
o Annual check of hepatitis B surface antibody (HBsAb) levels and be revaccinated if antibody titres fall below 10 mIU/mL
o Should not receive live attenuated vaccines.
· CMV prophylaxis and treatment:
o Prophylaxis for 3-6 months, until immunosuppression has been reduced to maintenance level.
o Monitoring of serology status and viral load should be available.
o In treatment mild and moderate CMV disease, oral valganciclovir and intravenous ganciclovir are of equivalent efficacy. However, in life-threatening CMV disease intravenous ganciclovir is indicated.
o Treatment duration according to the viral load.
· BK nephropathy prophylaxis and treatment:
o Should be suspected in any case of acute graft dysfunction, screening by urine microscopy for decoy cells or by PCR on urine or serum.
o Confirmation by renal biopsy (2 cores involving medullary tissues and stain with SV 40) .
o If PCR revealed BKV load exceeds 104 copies/ml…reduction of immunosuppression therapy is indicated (no specific therapy for BK virus).
· Pnumocysis jirovecii prophylaxis and treatment:
§ co-trimoxazole 480mg daily for 3-6 months.
Level of evidence; V (consensus guidelines)
Guide lines of postoperative care in kidney transplant recipients
o Outpatient follow up organisation
· KTR infrastructure follow up includes
Availability of a consultant in a dedicated outpatient area having an access to rapid lab results within 24 h also with rapid access to MDT when needed ,the principles of treatment need to be planned according to the National Service Framework and Kidney Health Delivering Excellence
· Clinic frequency
Uncomplicated cases can be followed less frequently .
First month post transplantation follow up can be for 2-3 times weekly
2-3months could be 1-2 times weekly
4-6 months can be every 2-4 weeks
6-12 months can be every 4-6 weeks
then it can be 3-6 monthly.
Patient need to have access to their data
· Chronic transplant care review
A detailed one need to be done annually postoperatively
o KTR non adherence
Factors leading to non adherence must be detected accompanied with early intervention
Children and adolescent pathways need to be clear.
o KTR immunosuppressive therapy
KTR: immunosuppression regimen
The patient need to be involved in the choice of immunosuppression induction and maintenance.
KTR: Induction immunosuppression
Immunosuppression started before or at the time of renal transplantation.
All cases must receive induction therapy which is IL2-RA in low immunological risk and T cell depleting antibodies for high immunological risk or when steroids and CNI are avoided.
KTR: Maintenance immunosuppression
Ø CNI is adviced to be started at transplantation time.
Ø For low immunological risk, CNI and antiproliferative agents with or without steroids .
Ø Low medium dose Tac can be used with steroids for cases at low risk of PTDM.
Ø Mycophenolic acid is the first-line anti-proliferative agent except in fertile cases who doesnot want contraception ,azathioprine can be used.
Ø If Tac is untolerable , cyclosporine ,sirolimus , everolimus, or belatacept can be used.
Ø Myfortic and MMF are equivalent immunosuppressives
Ø For low immunological risk cases steroid avoidance or withdrawal can be the policy in the first week post transplantation.
Ø In uncomplicated RT after 3 months, minimum CNI target levels can be used without withdrawing it.
Ø Low doses of steroids can be continued if steroids is not withdrawn in the first month.
Ø Monitoring immunosuppressives is needed
Tac and ciclosporin should be monitored trice a week 1st week after trnasplanation
Tacrolimus is monitored by the C0 trough level, while ciclosporin either by trough
(C0) or 2-hour post dose (C2) level
Sirolimus need to be monitored by the C0 trough level
Ø Only generic agents approved by the European Agency for the Evaluation of Medicinal Products can be used.
o Acute rejection
Ø Renal biopsy is done before diagnosing acute rejection unless it will delay therapy
Ø 16 gauge automated core biopsy needle is used with 2 cores .
Ø Protocol transplant biopsy can also be needed while C4d and SV40 staining should be performed
Ø HLA have to be sent at the biopsy time.
Ø The first line of therapy of acute cellular rejection is intravenous corticosteroids then maintenance including steroids as well.
Ø For refractory acute cellular rejection lymphocytic depleting agent can be used.
Ø AMR treatment includes steroids; plasma exchange; IVIg ; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib.
Ø After rejection episode MPA-based immunosuppression need to be used.
o Chronic Allograft injury
-Early detection is mandatory for prompt intervention.
-serum creatinine and urine albumin creatinine ratio must be followed up in each visit.
– Renal biopsy stained for C4d and
SV40 is the best investigation for deterioration of renal function
It can be done 7-10 days during DGF or with new onset of protienuria
-HLA antibodies need to be sent at the biopsy time
– for the treatment if CNI toxicity is detected ,CNI has to be withdrawn ,with maximising immunosuppressive therapy if there is evidence of immune injury.
o KTR: Cardiovascular disease and lifestyle
§ HTN
-BP should be recorded each visit ,targeted <140/90 along with home ambulatory BP monitoring .
-RAS blockers are best for proteinuria but must be used carefully in the first 3 months .
-Renal atretery stenosis can be the cause of resistant HTN
§ Dyslipidemia
-Fasting lipids levels should be monitored twice per year
– Statin therapy is used to decrease cardiovascular risk in patients with primary or secondary risks
-High simvastatin doses must be avoided with ciclosporin and CCB
§ DM
-PTDM need to be screened for each visit
– Immunosuppressive choice must consider the DM development risk
-PTDM need to be diagnosed and treated according to a protocol.
– diabetic recipients need to undergo screening for DM complications
§ Ischemic heart disease
– Transplant recipients can receive standard IHD treatment
– Smoking must be discouraged in transplant recipients
§ Lifestyle
Maintaining healthy lifestyle measures is essential including healthy diet , targeted weight
Avoid alcohol and recreational drugs and over the counter drugs and herbs
§ Neoplasia
-screening for cancer
Must be similar to general population as cancer cervix , breast , colon ,prostate
Patient must be aware of malignancy risks and report suspicious symptoms
Skin surveillance and hepatic US ,alpha fetoprotein for cirrhotic cases
-Nonmelanoma skin cancer
Recipients must be oriented about the hazards of sun exposure, use sunblock with high SPF
Biannual assessment by a specialised physicion for 1st 5 years then annually
Acitretin is adviced as chemoprophylaxis for those with ≥2 previous NMSC
Immunosuppresion need to be reduced in such case and m TORI can be used for cases with denovo malignancy specially Kaposi sarcoma.
o Infection complications
– Vaccines
Inactivated viral vaccines is recommended in KTR as well as annual influenza vaccine
HBsAb titer follow up if decreased revaccination is needed
Avoid live attenuated vaccines
Pneumococcal vaccine /5y
-CMV disease
Viral load and CMV Ab need assessment for donor and recipient
Prophylaxis therapy for 3-6 months and treatment for 6 weeks after TDA therapy
IV ganciclovir for lifethreatening CMV infection and oral valganciclovir for moderate cases
– EBV disease
PTLD occurrence necessitate withdrawal or reduction of immunosuppression
Both donor and recipient must have the EBV serological level recorded , and for high risk cases EBV viral load needs monitoring as immunosuppression will be reduced with high EBV titers
-VZV infection
IV Aciclovir or oral valaciclovir is used for primary infection treatment until the lesions scab over
Oral acyclovir or valaciclovir can be used for uncomplicated shingles.
Invasive shingles or with ocular involvement need to be treated with IV acyclovir and reduction of immunosuppression
VZV IgG negative cases with primary exposure should receive IVIG best within 96 hours, but up to a maximum of 10 days after exposure.
VZV IgG negative cases need to be vaccinated before transplantation
-HSV infection
Superficial lesions can be treated with oral acyclovir while systemic can be treated with IV acyclovir till lesions resolve with reduction of immunosuppression and oral for 14 days
Oral prophylaxis can be given for cases with recurrent infection
-BKV nephropathy
Can be treated with immunosuppression reduction.
It is suspected with unexplained deterioration of renal function.
Diagnosed by renal biopsy stained with SV40 screened for by BKV viral load or by urine microscopy for decoy cells or by PCR on urine or serum.
– Pneumocystis jirovecii infection
Treated by oral or IV cotrimoxazole for 14-21 days or pentamidine if cotrimoxazole is contraindicated .
-Post transplant infection prophylaxis
co-trimoxazole 480 mg daily for 3-6 months daily
oral antifungal prophylaxis for 1 week after transplantation
for certain cases TB prophylaxis with INH is needed for 6 months post transplantation
-HEV
Screening should be done
o Bone and joint disease
-Osteoprosis
DEXA scan can be done if e GFR >30 ml/min/1.73m2
Steroid free immunosuppressive regimens
better be applied in cases with or at high risk of osteoporosis.
Treated according to RTP guidelines for steroid induced osteoporosis
– Tertiary hyperparathyroidism
Severe cases need to be treated before transplantation as in CKD cases
– Gout
Avoid using allopurinol or febuxostat with azathioprine
Avoid NSAID
Acute gout can be treated with oral prednisolone course
Colchicine is effective in gout in KTR
– Calcineurin inhibitor bone pain
CNI better avoided
Dihydropyridine calcium antagonists can be used
o Hematological complications
-Anemia
Have to be manged as CKD cases
-Polycythemia
Initially treated with ACEI or ARBs
Treatment is according to hematocrit and PCV
Venesection is used in refractory cases
o Reproductive issues
-Conception and contraception in females
MPA drugs , m TORI need to be stopped before conception.
Conception can be possible after 1 year of transplant with stable kidney function
Fertility counselling is mandatory before transplantation as well as breast feeding counselling after delivery
Contraception counselling as general population
KTRs need to take aspirin 75 mg daily from 12 weeks gestation to decrease pre-eclampsia risk
– Conception and contraception in male
m TOR I is the only immunosuppressive that need to be avoided in males otherwise they can bank their sperms before starting the drug
MPA use have to balance risk against benefit
– Sexual dysfunction has to be treated with access to local andrology services
Audit measures details for the Post-operative Care of the Kidney Transplant Recipient must be recorded
Rationale for Clinical Practice Guidelines for Post-Operative Care of the Kidney Transplant Recipient
Infrastructure need to be in place for KTR follow up in a standardized organised manner with easy accessibility
-level of evidence is V
Summary of the Article;
Introduction;
Guidelines;
Level of evidence ((V))
These guidelines cover the period after renal transplantation, specifically from initial hospital discharge until graft failure or patient death.
The management of KTR can be divided into two phases:
a. Early post-operative phase when prevention of AR and opportunistic infection, optimization of graft function.
b. Later phase to preserve good graft function, ensure medication adherence, and prevent
the long-term consequences of IS – malignancy, infection and premature CVD.
Management of the early and late phase complications of transplantation requires monitoring at reducing the frequency, awareness of complications, access to the investigation, and strategies for preventing and treating complications.
KTR- Organization of Outpatient Follow-up:
Clinic infrastructure:
-Consultants should be available for every clinic.
– Dedicated outpatient area
– Availability of results of blood tests within 24 hours
-Access to an MDT
Clinic frequency:
2-3 times weekly for the first month after transplantation
1-2 times weekly for months 2-3
Every 2-4 weeks for months 4-6
Every 4-6 weeks for months 6-12
3-6 monthly after that
Patient access:
-On-line access to their results
-Open access to outpatient service and established point of contact for enquiries
-Patient information should be available in both written and electronic formats
Chronic transplant care review
-Detailed review should be performed annually post-operatively in parallel with a formal medical review.
Non-adherence
Recognizing non-adherence
-Prevent and detect non-adherence, and factors associated in KTR.
-Established interventional pathway for nonadherence
Immunosuppressive treatment
Induction immunosuppression
– IS drugs should be started before or at the time of KT to all KTRs, and their choice according to immunological risk either IL2-RA or T-cell depleting antibodies.
CNI should be started at the time of transplantation and not delayed until the graft is functioning
Maintenance immunosuppression
-Normally consist of CNI, and anti-proliferative agent, +/- corticosteroids in low and medium risk KTR
-Tacrolimus (trough target 4-8 ng/mL) is recommended in low and medium risk and are not at high risk of PTDM.
– Anti-proliferative agent: MPA-based drugs should be the first-line in preference to azathioprine.
– Slow release tacrolimus for patients who suffer intolerable SE.
– If tacrolimus was not tolerated for SE to considere for the use of ciclosporin, sirolimus, everolimus, or belatacept
-MMF and enteric-coated MPA provides equivalent maintenance immunosuppression.
-Steroid avoidance or steroid withdrawal in low immunological KTR
– To aim for minimum target levels for CNIs after 3 months in uncomplicated renal transplantation
-CNIs should not be withdrawn.
-If steroids are not withdrawn to be continued at low dose (prednisolone 5 mg per day or less).
Monitoring of immunosuppression
-CNI level should be monitored, initially should be three times a week.
-Levels should be checked when adding new medication, change the dosage or in unexplained graft dysfunction
-Tacrolimus monitored by the trough (C0) level, while ciclosporin by either C0 or C2 level
– Result should be available within 24 hours
-The utility of monitoring MPA C0 levels is uncertain
– Sirolimus monitored by the C0 trough level
Prescribing and the use of generic agents
-Generic IS compounds should not be used
– KTRs should be aware about importance of not switching
-Drugs should be prescribed by brand name
-Closely monitored after switching between generic preparations until a new steady state is established.
Acute rejection
Diagnosis of acute rejection
-Renal biopsy should be carried out before treating an AR unless this will delay treatment or pose a significant risk.
-Two cores of renal tissue should be obtained.
-Using16 gauge automated core biopsy needle recommended.
-Protocol transplant renal biopsy might be considered.
– Use of C4d and SV40 staining should be performed upon transplant biopsies
– At the time of renal biopsy send for HLA-specific antibodies.
Treatment of acute rejection
-Borderline ACR should be treated in the context of acute graft dysfunction
-High dose IVMP should be the first line treatment for ACR
-Maintenance steroids should be added or restarted in steroid-free patients with ACR.
– lymphocyte depleting agents in refractory ACR or aggressive vascular CR
-AMR should be treated with steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting agent or bortezomib
-After an episode of rejection azathioprine should be switched to MPA-based IS, MPA should be started or maximized.
Chronic Allograft Injury
Diagnosis of Chronic Allograft Injury
-Proactive and systematic approach should employed to manage graft dysfunction.
-Renal function should be monitored at each clinic visit by serum creatinine and PCR or ACR.
-Biopsy is the optimal investigation
-Biopsies should be stained for C4d and SV40
-At the time of renal biopsy to send for HLA-specific antibodies (2C)
Treatment of chronic allograft injury
-CNI withdrawal if there is evidence of CNI toxicity or non-specific IFTA.
-Intensification of IS if there is evidence of ongoing immune injury.
Renal biopsy in chronic allograft injury
-If there is a persistent unexplained elevation of creatinine or failure to return to baseline
– After an episode of biopsy proven acute rejection (BPAR)
-Every 7-10 days during DGF
-Renal function is not achieved within 4-8 weeks.
-New onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol).
Cardiovascular Disease and Lifestyle
Hypertension
-BP should be recorded at each clinic visit.
-Clinic BP should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35)
– Home BP & ABPM lower BP targets <135/80mmHg
– Effort should be focused on achieving absolute BP control
– RAAS Inhibitors may be more effective in reducing proteinuria.
-Resistant HTN may be due to TRAS
Dyslipidemia
-Fasting lipid levels should be measured annually
– Target is the same as in the general population.
– Statin therapy to reduce the risk of CAD.
– High dose simvastatin (≥40mg daily) should be avoided in conjunction with CCB or ciclosporin.
Diabetes mellitus
-Screening for PTDM by dipstick urinalysis and BSL level at each clinic visit.
-Choozing IS should take into account risk for diabetes development
-PTDM diagnosis is made based on WHO criteria, once established on stable maintenance IS
-PTDM should be managed with specialists in diabetic medicine
-Screening for diabetic complications using guidelines for non KTR patients with diabetes
Ischemic heart disease
-Standard treatment for IHD, including thrombolysis, revascularization, and secondary prevention.
Smoking cessation
-Smoking should be strongly discouraged.
Lifestyle measures
-Advice on healthy lifestyle; healthy diet, target ideal BW and BMI, physical activity, avoid alcohol and recreational drugs, discourage the use of OTC drugs.
Neoplasia
Screening for cancer
-Screening should be similar to the general population for cervical, breast, colon and prostate cancer
-Screening is not recommended for RCC
-Patients should be aware of malignancy risk.
-Skin surveillance by a healthcare professional at least biannually up to 5 years post-transplant and annually from 5 years post-transplant
-Patients with cirrhosis ;an annual hepatic US and AFP
Non-melanoma skin cancer (NMSC)
-Educated about the adverse effects of sun exposure, to use total sunblock SPB ≥50.
-Encourage self-examination, and at least biannual by trained healthcare professional up to 5 years post-transplant and annual review from 5 years.
– Prescription of acitretin as chemoprophylaxis if ≥2 previous NMSC
Immunosuppression in cancers
-IS should be reduced if neoplasia develops.
– m-TORi) are considered as alternative IS if developed de novo malignancy, also, have specific effects in Kaposi sarcoma
Infection Complications
Vaccination
KTRs should be vaccinated with inactivated viruses, annual influenza vaccination unless contraindicated (
-HBsAb levels rechecked annually and be revaccinated if titres fall below 10 mIU/mL
-Should not receive LAV
-Pneumococcal vaccine and a booster every five years.
Cytomegalovirus (CMV) disease
Prophylaxis and treatment of CMV disease
-Prophylaxis should be continued for 3-6 months, until IS has been reduced to maintenance level
-Treatment to be administered for 6 weeks after treatment with a TDA
-Donor and recipient CMV status should be recorded at the time of transplantation
-For mild and moderate CMV disease, oral valganciclovir and IV ganciclovir are of equivalent efficacy
-For life-threatening CMV disease IV ganciclovir recommended.
-Duration should be determined by monitoring viral load
Epstein Barr Virus (EBV) infection
-IS to be reduced or stopped following the development of PTLD.
-Both donor and recipient EBV serology should be recorded at the time of transplantation
-All high risk (D+/R-) should have EBV viral load measured immediately after transplantation, monthly for 6 months, and 3 monthly to one year.
– EBV viral load monitoring at time of rejection
-IS should be reduced when EBV titres rise significantly
Varicella Zoster Virus (VZV) infection
-Primary infection; treated with IV aciclovir or oral valaciclovir until the lesions scab over.
– Uncomplicated shingles; treated with oral acyclovir or valaciclovir until the lesions scab over
-Disseminated (>2 dermatomes), ocular or invasive shingles should be treated with IV aciclovir until
with a reduction in IS.
-Varicella-susceptible KTRs with primary exposure to VZV should receive IVIG, If unavailable oral aciclovir
-VZV IgG negative should be vaccinated prior to transplantation
-IS should be reduced during primary infection
Herpes Simplex Virus (HSV) infection
-Superficial HSV infection; treated with oral agents
-Systemic HSV infections; treated with IV aciclovir and a reduction in IS
– Recurrent HSV infection; oral prophylaxis
BK virus (BKV) nephropathy
-Should be treated by reduction in IS.
-Screening when unexplained deterioration of renal function by viral load or by urine microscopy or PCR
– Suspicion to be confirmed by renal biopsy, including SV40 stain.
-IS should be reduced when the serum BKV load exceeds 104 copies/ml
Pneumocystis jirovecii infection – treatment and prophylaxis
-All confirmed cases should be treated for 14 to 21 days with co-trimoxazole orally or IV.
-Pentamidine if there is contraindications to co-trimoxazole.
– In severe disease consider glucocorticoid
-All KTR should receive 3-6 months co-trimoxazole 480mg daily for PCP prophylaxis
-Oral antifungal prophylaxis for one week after transplantation
– TB prophylaxis against with daily INH with pyridoxine for 6 months after transplantation in selected cases.
Hepatitis E Virus (HEV)
Screened blood components should be given to all KTR
Bone and Joint Disease
Osteoporosis
-KTRs with osteoporosis to consider for steroid-avoiding IS
-KTRs on long-term steroids or at high risk for osteoporosis should undergo DEXA scanning if eGFR >30 mL/min/1.73m2 .
-Treatment according to the RCP guidelines for steroid-induced osteoporosis
Tertiary hyperparathyroidism
-Severe hyperparathyroidism should be treated prior to transplantation
– Cinacalcet can be used in KTR
-Treatment should be the same as for other patients with CKD
Gout
– Neither allopurinol nor febuxostat should be administered with azathioprine
-Hyperuricaemia should be treated when associated with gout, tophi or uric acid stones
-NSAIDs) should be avoided in KTRs
-Acute gout; treated with brief a course of oral prednisolone.
-Colchicine is an effective treatment for gout in KTR
Calcineurin inhibitor bone pain
-Reduction or withdrawal of CNIs when intractable bone pain.
-Dihydropyridine calcium antagonists also may be beneficial
Haematological Complications
Anemia:
-Chronic anemia; managed as other patients with CKD
Polycythemia
-Initial treatment ACEIs or ARBs.
-Treatment initiation if the Hct exceeds 52% in men and 49% in women
-Venesection may be used in refractory cases
Reproductive Issues
Conception and contraception (female)
-MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately.
– m-TORi should be stopped prior to conception and replaced
– KTRs should wait for one year and have stable function before attempting conception
– KTRs receive aspirin 75 mg daily to reduce the risk of pre-eclampsia from 12 weeks gestation until birth
-Contraception advice should be similar to the general population
Conception and contraception (male)
MPA containing have theoretical teratogenic potential in men.
m-TORi reduce the male sperm count
All immunosuppressive drugs other than m-TORi can be used in male KTRs.
Sexual dysfunction
-Care pathways for dealing with sexual dysfunction should be established
-Close liaison with local andrology service is recommended
– Sildenafil is safe and effective in male KTR not taking nitrates
Level 5
VII. Post-Operative Care in the Kidney Transplant Recipient (BTS GUIDELINES- 2017)
1.Summarise this article
These guidelines are useful to all those involved in the care of KTR who are non-experts, & to trainees (medical surgical), general practitioners, nurse specialists & others.
The period covered is from KTX (initial discharge) until graft failure or patient death.
KTR management phases:
1.Early post-op: involves prevention of AR & opportunistic infections, & optimizing graft function.
2.Later phase: to ensure good graft function, adherence to & prevention of long-term IS therapy effects (malignancy, infection & CVD)
Management of complications of TX requires regular monitoring, awareness of complications, access to investigation, & strategies for prevention & treatment of complications.
The modified GRADE system was used in these guidelines.
Summary of Post-Operative Care of the KTR
1. Outpatient Follow-up
Clinic infrastructure
A consultant should be available
A dedicated outpatient area
Blood tests results available & reviewed within 24 hr
Access to a MDT (pharmacist, dietician, social worker & psychologist)
Clinic frequency
Uncomplicated KTR reviewed progressively less frequently (2C)
Patient access
All KTRs should have an open access to support services & results. (2C)
Chronic TX care review
A detailed patient-centered review done annually post-op (2C)
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2.Non-adherence
Recognize & prevent non-adherence in KTR. (2C)
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3.Immunosuppressive treatment
Regimen
KTR &/or carer engaged in the selection of induction agent & maintenance IS (1D)
Induction IS
IS drugs started before or at the time of KTX (1B)
Biological agents for all; IL2-RA (low immunological risk) or TDAs (higher risk) (1B)
TDAs for steroid or CNI avoidance regimen in lower risk KTRs (1C)
· CNI started at the time of TX & not delayed until the graft is functioning (2C)
Maintenance IS
·Should consist of a CNI & an anti-proliferative agent +/- corticosteroids in low & medium risk KTRs (1B)
·Tac (trough 4-8 ng/mL) is the CNI of choice in KTRs also taking steroids who are low & medium immunological risk & are not at high risk of developing PTDM) (2C)
·MPA -based drugs are 1st-line anti-proliferative in preference to AZA, EXCEPT in fertile KTRs not willing to use reliable contraception (2B)
Slow release tac is an option for those intolerant to S/Es related to peak dose toxicity (2C)
·Use of 2nd-line agents (cycl, sirolimus, everolimus, or belatacept) considered for KTRs intolerant to tac or suffer serious S/E related to its use (1B)
·MMF& EC-MPA provide equivalent maintenance IS (2B)
·Steroid avoidance/withdrawal can be used during the 1st post-TX week in low risk KTRs (2B)
·Aim for minimum CNIs targets in uncomplicated KTRs after 3 months (2C)
·CNIs should not be withdrawn (2B)
·If steroids not withdrawn within 1stmonth, they should be continued at low dose (pred=/< 5 mg/ day) (2C)
Monitoring of IS
·CNI levels should be monitored; initially 3 times a week.
·Check levels when any new medication is added, dosage or formulation is changed, or if unexplained graft dysfunction occur (2C)
·Tac monitored by trough (C0); cycl by either C0 or 2-hour post dose (C2) level (2C)
·Levels should be available within 24 hours in the 1st 3 months after TX (2D)
·Utility of monitoring MPA C0 levels is uncertain (2D)
·Sirolimus monitored by the C0 trough level (2C)
Use of generic agents
·Should not be used unless bioequivalent & approved the EAEMP (2D)
·KTRs made aware of their existence & not to switch between preparations without supervision (2D)
·Drugs prescribed by brand name (2D)
·Close monitor after switching between generic preparations until a new steady state reached (2D)
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4. Acute rejection
Diagnosis
Biopsy before treating unless undue delay or significant risk to the patient (1C)
2 cores of renal tissue obtained at biopsy to increase the sensitivity (2C)
A 16 gauge automated needle is used where possible (1C)
A protocol biopsy in the setting of persisting DGF (1C)
Routine C4d & SV40 staining done on biopsies to address other causes of graft dysfunction (2C)
Sample sent at the time of renal biopsy (for graft dysfunction) for HLA-specific antibodies (2C)
Treatment
Borderline ACR should be treated in the context of acute graft dysfunction (2D)
High dose IV corticosteroids is the 1st-line treatment for ACR (1D)
Maintenance steroids added or restarted in steroid-free patients undergoing AR (any type) (2D)
TDAs for refractory ACR or aggressive vascular cellular rejection (Banff 4 Type II & III) (2C)
AMR treated with =/> 1 of the following: steroids; PE; IVIG; anti-CD20 antibody, TDAs or bortezomib (2C)
BTS guidelines on Ab-incompatible TX for management of rejection in the context of Ab-incompatible TX (1A-D)
After rejection – AZA switched to MPA, MPA started, or dose of MPA maximized (2D)
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5.Chronic Allograft Injury
Diagnosis
Early detection to maximize the potential for intervention. A proactive & systematic approach to manage graft dysfunction (1C)
Renal function monitored at each visit by assessment of creatinine & urine protein dipstick, followed by PCR or ACR if positive (2C)
Biopsy is the optimal test for parenchymal causes of graft dysfunction where the cause is uncertain (2C)
Biopsies should be stained for C4d & SV40 (2C)
HLA specific antibodies tested at the time of renal biopsy (for graft dysfunction) (2C)
Treatment
Withdraw CNIs if evidence of toxicity or non-specific IF/TA (2C)
Intensify IS if ongoing immune injury (cellular rejection &/or humoral rejection) (2C)
Preventive strategies similar to other CKD patients (2D)
Renal biopsy
Is indicated:
If persistent unexplained rise of creat or failure to return to baseline after a BPAR (1C)
Every 7-10 days during DGF (2C)
If expected renal function is not achieved within 4-8 weeks (2D)
If sustained new onset proteinuria develops (PCR >50 mg/mmol or ACR >35 mg/mmol) (2C)
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6. CVD & Lifestyle
Hypertension
BP should be recorded at each visit (1C)
BP should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
Home BP recordings & 24-hour ambulatory recordings help in some instances but lower BP targets should then be set (<135/80mmHg) (2D)
No any antihypertensive agent is better than any other & effort focused on absolute BP control rather than the use of individual agents (2D)
Inhibitors of the RAS may be more effective in the minimisation of proteinuria but should be used with caution in the 1st3 months post-TX (2C)
Resistant HTN may be due to TX renal artery stenosis & investigated according to local practice (2D)
Dyslipidaemia
Fasting lipid levels should be measured annually (2C)
Treatment targets same as in general population (2C)
KTRs at increased primary or secondary CV risk receive statin to reduce the risk of CAD (2C)
The choice & dose of statin should consider concurrent IS. High dose simvastatin (≥40mg daily) avoided in conjunction with Cycl &/ CCBs (2D)
Diabetes mellitus
Screening for PTDM by dipstick urinalysis & blood sugar level at each visit (2C)
Post-TX IS should consider risk factors for the development of diabetes (2C)
Diagnosis of PTDM is based on WHO criteria for the diagnosis of DM based on fasting or random blood, HBA1c or OGTT (1C)
PTDM diagnosis is made once KTRs are established on stable maintenance IS (2D)
PTDM should be managed in collaboration with specialists in diabetic medicine (2D)
All units should have a protocol for the management of PTDM (2C)
KTR with diabetes (either prior to TX or PTDM) should be screened for diabetic complications in line with guidelines for non KTR patients with diabetes (2D)
Ischaemic heart disease
KTRs should receive standard treatment, including thrombolysis, revascularisation, & secondary prevention (2C)
Smoking cessation
Smoking should be strongly discouraged in KTRs (1A)
Lifestyle measures
Advice on healthy lifestyle is a routine part of post-TX care:
Maintenance of a healthy diet encouraged (2C)
Ideal weight targeted (BMI ≤25 kg/m2) (2C)
Weight management services should be available (2C)
KTRs should participate in physical activity appropriate to age & comorbidity (2D)
Alcohol intake within national guidelines (2D)
Recreational drug avoided (2D)
OTC medications & herbal medicines discouraged (2D)
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7. Neoplasia
Screening
Similar to general population for cervical, breast, colon & prostate cancer (2C)
Not recommended for RCC (2C)
Patient education pre & post-TX (1C)
KTRs should be aware of malignancy risk and encouraged to report symptoms (2D)
Skin surveillance biannually up to 5 years & annually from 5 years post-TX (2C)
Cirrhotic KTRs should have annual hepatic USS & alpha fetoprotein (2C)
Non-melanoma skin cancer
KTRs educated about A/Es of sun exposure (1C)
Individualized assessment according to risk factors (2C)
KTRs encouraged to cover skin in direct sunlight & to use total sun-block (1D)
Self-examination encouraged with guidance provided (2C)
Acitretin as chemoprophylaxis for those with ≥2 previous NMSC (2B)
Immunosuppression in cancers
IS reduced if neoplasia develops (2C)
m-TORi as alternative IS in KTRs who develop de novo malignancy (2C)
Immunosuppression in KS
m-TORs have specific anti-tumour effects (2C)
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8. Infection Complications
Vaccination
With inactivated viruses as in normal population (1D)
Annual influenza vaccination (1C)
HBsAb rechecked annually & revaccinate if Ab titres fall < 10 mIU/mL (2D)
Live attenuated vaccines not given (2C)
Pneumococcal vaccine & a booster every 5 years (2D)
Prophylaxis & treatment of CMV disease
Prophylaxis for 3-6 months (1B)
Treatment for 6 weeks after treatment with a TDA (1C)
Measure CMV serological status & quantify viral load (2D)
Donor & recipient status recorded at the time of TX (2D)
A written protocol based on prophylaxis or pre-emptive therapy (2D)
For mild & moderate disease, oral valganciclovir & IV ganciclovir are equivalent (2C)
IV ganciclovir is 1st choice in life-threatening disease (2D)
Treatment duration determined by monitoring viral load (2C)
EBV infection
IS reduced or stopped following PTLD (1C)
Serology recorded at the time of TX for donor & recipient (2D)
D+/R- KTRs: viral load checked immediate after TX, monthly for 6 mo, & monthly to 1 year (2C)
Viral load monitored after the treatment of rejection (2C)
IS reduced when titers rise significantly (2C)
VZV infection
Chickenpox treated with IV aciclovir or oral valaciclovir (1C)
Uncomplicated shingles treated with oral acyclovir or valaciclovir (1D)
Disseminated, ocular or invasive shingles treated with IV aciclovir & reduce IS (1B)
Susceptible KTRs given IVIG (1D)
Patients on waiting list who are IgG -ve vaccinated prior to TX (2D)
IS reduced during primary infection (2D)
HSV infection
Superficial infection treated with oral agents (1D)
Systemic infections treated with IV aciclovir & a reduction in IS (1C)
BK nephropathy
· Treated by reduction in IS (1D)
Screening if unexplained renal function deterioration (2D)
Screened for viral load or by urine microscopy for decoy cells or by PCR on urine or serum (2C)
Diagnosis confirmed by renal biopsy (stained for SV40) (2D)
IS reduced when BKV load > 104 copies/ml (2C)
No established specific treatment (2D)
Re-TX can be safe in those who have BK nephropathy in an earlier graft (2C)
Pneumocystis jirovecii infection
Treated for 14 – 21 days with co-trimoxazole orally or IV (2B)
Pentamidine if contraindication co-trimoxazole (2B)
Adjunctive glucocorticoid in severe disease (2D)
Post-transplant infection prophylaxis
3-6 months of co-trimoxazole 480 mg daily (1B)
Oral antifungal for 1 week after TX (2C)
Mycobacterium TB prophylaxis (daily INH for 6 months) in selected cases (2C)
Hepatitis E Virus (HEV)
HEV-screened blood components given to all KTR (1C)
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9. Bone & Joint Disease
Osteoporosis
Steroid-avoiding IS considered (2D)
DEXA scanning if eGFR >30 mL/min/1.73m2 (2D)
Treatment according to the RCP guidelines for steroid-induced osteoporosis (2D)
Tertiary hyperparathyroidism
Severe disease should be treated prior to TX (2D)
Cinacalcet can be used in KTR (2C)
Treatment same as for other CKD patients (2D)
Gout
Neither allopurinol nor febuxostat used with azathioprine (1C)
Hyperuricaemia treated if associated with gout, tophi or uric acid stones (2D)
NSAIDs should be avoided (2D)
Acute gout treated with a course of oral prednisolone. (2D)
Colchicine is effective for gout (2D)
CNI bone pain
Reduce or withdraw if intractable bone pain (2D)
Dihydropyridine CCBs may benefit (2D)
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10. Haematological Complications
Anaemia
Treated similar to other patients with CKD (2D)
Polycythaemia
Treated with ACEIs or (ARBs) (1C)
Haemoglobin monitored at every visit (2D)
Treatment if PCV >52% in men & 49% in women (2D)
Venesection in refractory cases (2D)
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11. Reproduction
Conception & contraception (female)
MPA stopped before pregnancy (1A)
Wait for 1 year before attempting conception (2C)
Counselling regarding fertility offered before or soon after TX (2D)
m-TORi replaced prior to conception (2D)
Pregnancy jointly managed with an experienced Obstetrician (2D)
Aspirin 75 mg/day to reduce risk of pre-eclampsia from 12 weeks gestation until birth (2C)
Risks & benefits of breastfeeding discussed (2D)
Conception & contraception (male)
MPA theoretically teratogenic (1D)
m-TORi reduce the male sperm count (1C)
Men who wish to maintain fertility should avoid m-TORi or bank sperm (2D)
Sexual dysfunction
Care pathways for sexual dysfunction should be established (2D)
Close liaison with local andrology service is recommended (2D)
Sildenafil is safe & effective (if not taking nitrates) (2D)
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2.What is the evidence provided by this article?
Level V
SUMMARY
Introduction
This document was designed to provide guidelines to the management of care of post kidney transplant recipient outside of the primary hospital where the surgery was performed. It covers care on the early post operative stage where the rate of graft rejection is very high and also care of the later phase when recipient is prone to chronic rejection of malignancies. Moreso, the document provides different grading system and evidence of practice for any opinion from the expects
KTR clinic infrastructure
KTR clinic frequency
Recognition of non-adherence
Induction immunosuppression
Maintenance immunosuppression
Diagnosis of acute rejection
Treatment of acute rejection
Treatment of chronic allograft rejection
Management of cardiovascular risk and disease
Life style measures
Prophylaxis against the following
Conception and contraceptives
The level of evidence is 1
Summarise this article
Introduction
These are clinical practice guidelines of Post-Operative Care in the Kidney Transplant Recipient; January 2017 (reviewed February 2022)
Cover the initial period of transplantation from hospital discharge until graft failure or patient death
The management of KTR is divided into two phases:
1. an early post-operative period when the risks of acute rejection and infection are high (3-6 months)
2. a later phase when the aims are to preserve good graft function, ensure adherence to medication, and prevent the long-term consequences of immunosuppression (> 3-6 months)
Outpatient Follow-up
Clinic infrastructure
A consultant should be available for every transplant clinic
Blood test results should be available within 24 hours
MDT including pharmacist, dietician, social worker and psychologist
Patient care should be planned
Clinic frequency
The first month (2-3 times weekly), 2-3 months (1-2 times weekly), 4-6 months (every 2-4 weeks), 6-12 months (every 4-6 weeks), and every 3-6 months after that
Patient access
All patients should have access to support services and results (on-line access, and open access to the renal transplant unit)
Information should be available in both written and electronic
Chronic transplant care review
Detailed review should be performed annually post-posttransplant and address concerns in medical, social, psychological and sexual domains
Renal dietician, social worker, specialist renal pharmacist and/or psychologist should be readily available
Non-adherence
Detect non-adherence with intervention for those at high risk of or with proven non- adherence
Immunosuppressive treatment
The patient and/or carer should be engaged in the decisions around selection of induction agent and maintenance immunosuppression (1D)
Induction therapy should be administered to all KTRs and should be started before or at the time of renal transplantation. IL2-RA for low immunological risk and TDAs for high risk (TDAs may also be useful for lower immunological risk patients with steroid- or CNI-free regimen
Maintenance immunosuppression consist of a CNI and an anti-proliferative agent, with or without corticosteroids in low and medium immunological risk KTRs (1B)
Low-medium dose tacrolimus (trough target 4-8 ng/mL) is recommended as the CNI of choice in patients also taking steroids who are low-medium immunological risk and are not at high risk of developing PTDM
Mycophenolic acid -based drugs should be the first-line anti-proliferative agent in preference to azathioprine, except in fertile KTRs who are unwilling to use reliable contraception
Slow release tacrolimus may be used as an option as second line agents for patients who suffer intolerable side effects related to peak dose toxicity (2C)
KTRs who are unable to tolerate tacrolimus can use the second line agents such as ciclosporin, sirolimus, everolimus, or belatacept
MMF Myfortic provide equivalent maintenance immunosuppression (2B)
Steroid avoidance or steroid withdrawal can be used during the first week after transplantation in low immunological risk kidney transplant recipients (2B)
The minimum target levels for CNIs in uncomplicated renal transplantation after 3 months (2C)
CNIs should not be withdrawn (2B)
If steroids are not withdrawn within the first month, then they should be continued at low dose (prednisolone 5 mg per day or less) (2C)
Long-term monitoring of immunosuppression levels is required
Drugs should be prescribed by brand name (whether branded or generic drugs are prescribed) (2D)
Acute rejection
Transplant renal biopsy should be carried out before treating an acute rejection episode unless this will delay treatment (16 gauge core biopsy needle and two cores of renal tissue)
Protocol transplant renal biopsyfor DGF (1C)
Do routine C4d and SV40 staining for biopsies to address other causes of graft dysfunction (2C)
Send serum sample at the time of renal biopsy for HLA-specific antibodies (2C)
Borderline acute cellular rejection should be treated in the context of acute graft dysfunction (2D)
High dose intravenous corticosteroids should be the first line treatment for acute cellular rejection (1D)
Maintenance steroids should be added or restarted in steroid-free patients undergoing acute rejection of any type (2D)
Lymphocyte depleting agents may be considered for refractory acute cellular rejection or aggressive vascular cellular rejection (i.e. Banff category 4 Type II and III) (2C)
AMR should be treated with one or more of the following modalities: steroids; plasma exchange; intravenous immunoglobulin; anti-CD20 antibody, lymphocyte-depleting antibody or bortezomib (2C)
After an episode of rejection (unless associated with low CNI levels) – azathioprine should be switched to MPA-based immunosuppression, or the existing dose of MPA maximised (2D)
Chronic Allograft Injury
Renal biopsy is the optimal investigation for parenchymal graft dysfunction where the cause is uncertain (2C)
Renal biopsies should be stained for C4d and SV40 (2C)
Serum sample should be sent for HLA- specific antibodies (2C)
Treatment by withdrawal of CNI if there is histological evidence of CNI toxicity and intensification of immunosuppression
Cardiovascular Disease and Lifestyle
Hypertension
BP should be <140/90 mmHg in clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
No evidence that any antihypertensive agent is better than any other
ACI/ARB is effective in proteinuria but should be used with caution in the first 3 months post-transplant. (2C)
Resistant hypertension may be due to transplant RAS
Dyslipidaemia
Do fasting lipid annual and the target is same as in the general population (2C)
Give statin risk of high risk of CAD (2C)
High dose simvastatin (≥40mg daily) should be avoided in conjunction with ciclosporin and/ calcium channel antagonists (2D)
Diabetes mellitus
The diagnosis of PTDM is made based on WHO criteria
KTR with diabetes should undergo screening for diabetic complications (2D)
IHD
Receive standard treatment for IHD, including thrombolysis, revascularisation, and secondary prevention (2C)
Smoking cessation
Smoking should be strongly discouraged in transplant recipients (1A)
Lifestyle measures
Maintenance of a healthy diet, ideal BMI ((BMI) ≤25 kg/m2), participate in physical activity, and avoid alcohol consumption, recreational drug and the use of over-the-counter medications
Neoplasia
Screening is similar to the general population for cervical, breast, colon and prostate cancer (2C)
Educate patient about the adverse effects of sun exposure
Patients should be encouraged to cover their skin in direct sunlight and to use total sunblock (Sun Protection Factor ≥50) (1D)
Reduce immunosuppression if neoplasia develops
m-TORi are alternative immunosuppressive agents in KTRs who develop de novo malignancy (2C) and have specific anti-tumour effects in Kaposi sarcoma (2C)
Infection Complications
Vaccination with inactivated viruses as per the normal population (1D). Influenza vaccination annually, HBV if HBsAb < 10 mIU/mL and pneumococcal vaccine and a booster every five years
Prophylaxis of CMV for 3-6 months. Do serology and viral load. The first line treatment of life-threatening CMV disease is intravenous ganciclovir
For EBV infection, reduce the dose of immunosuppression. Do serology for both donors and recipients, and high risk should have EBV viral load measured immediately after transplantation, monthly for six months, and three monthly to one year
Patients on the waiting list who are VZV IgG negative should be vaccinated prior to transplantation and. Reduce the dose of immunosuppression
Systemic HSV infections should be treated with intravenous aciclovir and a reduction in immunosuppression until a response occurs and oral medication should be continued for at least 14 days (1C)
For confirmed BK nephropathy reduce the dose of immunosuppression
Other infections are pneumocystis jirovecii infection and HEV
Bone and Joint Disease
Osteoporosis: steroid-free regimen for high risk patients and do DEXA scanning if eGFR >30. Treatment according to RCP guidelines for steroid-induced osteoporosis (2D)
Tertiary hyperparathyroidism: Treatment is the same as for other patients with CKD/cinacacet
Gout: not give allopurinol or febuxostat with azathioprine (1C). treat with predisolone/ colchicines and avoid NSAIDs
CNI bone pain: reduce the dose/dihydropyridine calcium antagonists
Haematological Complications
Anaemia: manage is the same as in CKD/ACEIs/ARBs
Polycythaemia: Venesection may be used in refractory cases
Reproductive Issues
Conception and contraception (female): wait for one year after transplant, counseling prior to transplantation, stop MMF/m-TORi prior to conception, and receive aspirin 75 mg daily from 12 weeks gestation
Conception and contraception (male): m-TORi reduce the male sperm count and counselled accordingly and/ theoretical teratogenicity for MPA containing compounds
Sexual dysfunction: Sildenafil is safe and effective in male KTR not taking nitrates (2D)
What is the evidence provided by this article?
Level 1 (Clinical practice guidelines)
I liked reading your summary and analysis. This is level 5 evidence, not level 1.
Ajay
Thank you sir
VII. Post-Operative Care in the Kidney Transplant Recipient (BTS GUIDELINES- 2017)
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1. Kidney Transplant Recipient (KTR) Clinic infrastructure
2. KTR: Clinic frequency
3.KTR: Patient access
.4.KTR: Chronic transplant care review
KTR: Recognising non-adherence
Kidney Transplant Recipient: Immunosuppressive treatment
Induction immunosuppression
Maintenance immunosuppression
KTR: Monitoring of immunosuppression
Acute rejection
Chronic Allograft Injury
KTR:Hypertension
KTR: Dyslipidaemia
KTR: Diabetes mellitus
KTR: Ischaemic heart disease
KTR: Smoking cessation
KTR: Lifestyle measures
KTR: Screening for cancer
KTR: Vaccination
KTR: Prophylaxis and treatment of CMV disease
KTR: EBV infection
KTR: Varicella Zoster Virus (VZV) infection
KTR: Herpes Simplex Virus (HSV) infection
KTR: BK virus (BKV) nephropathy
KTR: Pneumocystis jirovecii infection – treatment and prophylaxis
KTR: Osteoporosis
KTR: Tertiary hyperparathyroidism
KTR: Treatment of gout
KTR: Calcineurin inhibitor bone pain
KTR: Anaemia
KTR: Polycythaemia
KTR: Polycythaemia
KTR: Conception and contraception (female)
KTR: Conception and contraception (male)
KTR: Sexual dysfunction
I liked reading your summary and analysis. This is level 5 evidence.
Ajay
Thank you very much Prof.Sharma
Yes, prof.
The level evidence is 5
Level of evidence is 5.
I liked reading your summary and analysis.
Ajay
Renal transplant health care facility should be consultant based with availability of MDT; investigation results including CNI level should be available within 24 hours and should be reviewed by health care professionals within also 24 hours of clinic visit in a dedicated outpatient clinic
Easy access to services is recommended that should include online access to the result of investigations
Non adherence should be evaluated by the health care professionals, with identification of risk factors and all efforts should be done to prevent this major problem
Renal transplant recipient and/or caregiver should be involved in the decision making regarding immunosuppression medication selection
Induction immunosuppression
Maintenance immunosuppression
Monitoring
In case of graft dysfunction (acute or chronic), the minimum investigations required includes
Renal biopsy is indicated in the following settings
Diagnosis (using renal biopsy) should be confirmed before starting treatment except if there is suspicion of rejection and there is expected harm with treatment delay
Treatment of AR
Chronic allograft dysfunction
Hypertension after kidney transplantation
Hyperlipidemia after kidney transplantation
DM after kidney transplantation
IHD after renal transplantation
Life style after renal transplantation
Malignancy after renal transplantation
Vaccination
CMV prophylaxis and treatment
EBV prophylaxis and treatment of PTLD
VZV infection
HSV infection
BK nephropathy
Pneumocystis jirovecii infection prophylaxis and treatment
Prophylaxis against other infections
Bone problems with transplantation
Treatment of hyperurecimia / gout
Haematological Complications
Conception and contraception (female)
Conception and contraception (male)
What is the evidence provided by this article?
I liked reading your summary and analysis. This is level 5 evidence, not level 1.
Ajay
Summary of Clinical Practice Guidelines for the Post-Operative Care of the Kidney Transplant Recipient:
Clinic building:
KTR follow-up (2D) requires the following infrastructure:
Every transplant clinic should have a consultant-level healthcare professional.
KTRs should be reviewed in a dedicated outpatient area Blood test results (including drug levels, if possible) should be available within 24 hours.
A formal mechanism should exist for results review by healthcare professionals within 24 hours of a clinical appointment.
A multidisciplinary renal team, comprising a pharmacist, nutritionist, social worker, and psychologist, should be available.
Patient treatment should be organized according to the National Service Framework and “Kidney Health Delivering Excellence.
Immunosuppression:
-Immunosuppressants should be started before or during kidney transplantation (1B)
-All KTRs need biological induction treatment. In low-risk patients, an interleukin-2 receptor antagonist is used (IL2-RA). T-cell-depleting antibodies (TDAs) may be given to high-risk patients (1B)
-Lower immunological risk individuals who want to avoid steroids or calcineurin inhibitors (CNIs) may benefit from TDA induction treatment (1C)
-We propose starting a CNI upon transplantation, not after the graft is functional (2C)
-In moderate and medium immunological risk KTRs, we prescribe a calcineurin inhibitor (CNI) and an anti-proliferative drug, with or without corticosteroids (1B)
-Low-medium dosage tacrolimus (trough goal 4-8 ng/mL) is indicated as the CNI of choice in patients already taking steroids who have low and medium immunological risk and are not at high risk of developing PTDM (2C)
-Mycophenolic acid-based medicines should be the first-line anti-proliferative treatment above azathioprine, except in fertile KTRs reluctant to take contraception (2B)
Acute rejection:
–Before treating acute rejection, we advocate a transplant kidney biopsy unless it would delay therapy or put the patient in danger (1C)
-We propose considering a protocol transplant renal biopsy in the context of persistent delayed graft function (1C)
-For acute cellular rejection, we prescribe high-dose intravenous corticosteroids (1D)
-Refractory acute cellular rejection or aggressive vascular cellular rejection (Banff category 4 Type II and III) may benefit from lymphocyte-decreasing drugs (2C)
-AMR should be treated with steroids, plasma exchange, intravenous immunoglobulin, anti-CD20 antibody, lymphocyte-depleting antibody, or bortezomib (2C)
-After rejection, azathioprine should be transferred to MPA-based immunosuppression, MPA should be begun, or the current dosage of MPA should be increased (2D)
Chronic Allograft Injury:
–At each clinic visit, renal function should be assessed by serum creatinine and urine protein excretion by dipstick, augmented by spot protein: creatinine ratio (PCR) or albumin: creatinine ratio (ACR) if positive (2C)
-Chronic allograft injury should be treated with:
Withdraw calcineurin inhibitors if histology shows CNI toxicity or non-specific interstitial fibrosis and tubular atrophy (2C)
By intensifying immunosuppression, if immunological damage (cellular or humoral) persists (2C)
Hypertension:
-Clinic blood pressure should be <140/90 mmHg in the clinic (130/80 mmHg if PCR >50 or ACR >35) (2C)
Dyslipidaemia-
– Treatment targets should be the same as in the general population (2C)
Diabetes mellitus:
-PTDM is diagnosed based on fasting or random blood, serum glycated hemoglobin (HBA1c), or oral glucose tolerance tests (1C)
Smoking cessation
We recommend that smoking should be strongly discouraged in transplant recipients.
Screening for cancer
–Screening should be similar to the general population for cervical, breast, colon, and prostate cancer (2C)
-Skin monitoring biannually up to 5 years post-transplant and yearly after 5 years (2C)
-We suggest that immunosuppression should be reduced if neoplasia develops (2C)
-We suggest that mammalian targets of rapamycin inhibitors (m-TORi) are considered alternative immunosuppressive agents in KTRs that develop de novo malignancy (2C)
CMV therapy and prevention
-Prophylaxis should be maintained for 3-6 months until immunosuppression is at a maintenance level (1B)
EBV
-We advocate reducing or stopping immunosuppression after PTLD (1C)
BK nephropathy
-We recommend that confirmed BK nephropathy should be treated by a reduction in immunosuppression (1D)
Conception and contraception (female)
– We recommend that MPA-containing immunosuppressant drugs should be stopped prior to conception and replaced appropriately (1A)
I liked reading your summary and analysis. This is level 5 evidence, not level 1.
Ajay
Summary
This article is about the post op care of kidney transplant patients, which includes identifying and diagnosing accurately symptoms of rejection and other issues that can affect graft and patient outcome, along with its appropriate treatment. Long term outcome is important and this is kept in mind while monitoring patient in the post operative phase. Since immunosuppression regimen plays a crucial role in the success or failure of the transplant and patient survival rates, it has special details that need to be followed.
The clinical practice guidelines include the following :
Level of evidence
This is clinical practice guidelines, hence level of evidence is 1.
This is level 5 evidence, not level 1.
Ajay
I liked reading your summary and analysis, Will you change your practice based on this article?
Ajay