1. A 51-year-old Afro-Caribbean CK4 secondary to sickle cell nephropathy, is known to be homozygous for sickle cell disease. He had many crises in the past triggered by sepsis and sometimes without any triggering event. He had many blood transfusions in the past. The last crisis was provoked by sepsis after an operation for priapism. He needs counselling for transplantation.
- What is the outcome of kidney transplantation in sickle cell disease?
- How do you manage his transplantation (pre, intra and postoperative)?
- Discuss immunosuppression?
- Would it be different if he was heterozygous (trait)?
Thank you, All,
Many of you did not mention the ideal level of HbS in this case and the role of exchange transfusion. This is one of the essential key points in this scenario.
The best answer was by Dr Sherif Yousef.
The target is to decrease Hb S to < 30 % to improve O 2 delivery, with a final Hb of 10 gram/dl (avoid Hb > 11gm/dl) to avoid increased blood viscosity, and this can be done in 2 ways:
Therefore, follow-up of Hb and Hb electrophoresis after therapy is recommended.
This patient had a Hb of 8.5 gm. His HbS came down to zero after multiple blood transfusions (HLA-specific).
There is a lack of consenssus on the best prac tices for pre op er a tive and peripartum transfu sions.
Hb level no less than 9 no more than 11
RCE goal of %HbS <30%.
British Guidelines on red cell transfusion in sickle cell disease
urgery Preoperative transfusion is recommended for SS patients undergoing medium risk surgery (Grade 1A).
Preoperative transfusion is recommended for SC patients undergoing medium risk surgery (Grade 1C).
Transfusion is recommended for sickle cell patients of all genotypes requiring high-risk surgery (Grade 1C).
All sickle cell patients with other genotypes undergoing surgery should be individually assessed, taking into account previous history and complexity of surgery, and a management plan should be formulated to include the need for transfusion (Grade 1C)
Particular care should be taken to ensure that all aspects of perioperative care, including oxygenation, hydration, warmth and anaesthetic and surgical technique, are optimised in all sickle cell patients undergoing surgery (Grade 1C).
For patients requiring emergency surgery, the urgency and complexity of the procedure should be taken into account in the timing of perioperative transfusion.
Simple transfusion should be given preoperatively if Hb <90 g/l provided this will not result in undue delay to surgery. If transfusion is likely to cause an unacceptable delay to surgery, it is reasonable to proceed to surgery while arranging to transfuse the patient intra- or post-operatively if necessary (Grade 1D).
This is around surgery
what about the other aspects of preparation.
IS
Infection and vaccines.
antibiotic and antiviral prophylaxis.
sensitisaion and induction.
Thank you professor
I am already answered this scenario 3 day ago but I repeated the part that professor Halawa asked us about
This was my previous answer
Compared with no SCD
One-year death-censored graft survival in SCD was lower than in non-SCD recipients (94% vs. 98%; p = 0.02),
whereas there was no significant difference in patient survival between SCD and non-SCD recipients (96% vs. 97%; p = 0.36).
Five-year death-censored graft survival in SCD was lower than in non-SCD recipients (71% vs. 89%; p < 0.001) ,
whereas five-year patient survival was comparable between the two groups (83% vs. 87%; p = 0.12)
Compared with DM and hypertension patients
SCD was significantly associated with lower death-censored graft survival compared to DM (HR 2.32; 95% CI 1.52–3.56, p < 0.001), and hypertension (HR 1.91; 95% CI 1.25–2.92, p = 0.003)
Pre operation
Intra operation
are all important for achieving good results.
postoperative period
Desensitization programs
(ATG – plasma exchange – Basiliximab or Alemtuzumab )
Maintenance therapy with Tacrolimus- MMF- prednisolone wich better will tappred to avoid his effects on this patient
The most important difference is the absence of blood transfusions in heterozygous patient
Therefore he doesn’t need the desensitization plan at least
Dear Dr Ghalia,
I enjoyed reading your extensive write-up. Scientifically it is very good.
Ajay
Blood transfusion in sickle cell disease (SCD)
Anemia
Anemia is treated with simple blood transfusion if
Treatment of severe vasoocclusive disease
Transfusion is indicated in critically ill patients with stroke, multiorgan failure and acute chest pain syndromes
Target is to decrease Hb S to < 30 % to improve O 2 delivery, with final Hb of 10 gram/dl (avoid Hb > 11gm/dl) to avoid increase blood viscosity and this can be done by 2 ways:
So … follow up of Hb and Hb electrophoresis after therapy is recommended
Preoperative preparation
Transfusion is indicated in all patients undergoing operation requiring anesthesia that will last for > 30-60 min such as repair of inguinal hernia repair, cholecystectomy, cardiac, intraabdominal thoracic and brain surgeries.
So perioperative measures that should be don in the current case are :
What are the specific vaccines to be taken?
What is the management of a SC crisis in a transplant patient?
What is the mode of action of hydroxy urea how long before TX should it start,
References
1- Up-to-date
Thank you, Sherif
This is an excellent answer; well done. This patient had Hb of 8.5 gm. His HbS came down to zero after multiple blood transfusions (HLA-specific).
Informative, thank you
What is the outcome of kidney transplantation in sickle cell disease?
Multiple studies have described better patient survival of these patients on kidney transplant than on hemodialysis.
So, sickle cell disease or trait should not be regarded as a contraindication to transplantation, at least from the patient and allograft survival standpoint.
How do you manage his transplantation (pre, intra and postoperative)?
Discuss immunosuppression?
These patients are highly sensitized because of multiple blood transfusions
Induction by ATG and triple immunosuppressant maintenance should be followed.
Hydroxyurea can replace MMF with the added benefit of increasing HbF
Steroid slowly reduced to decrease events avascular necrosis of hip
Would it be different if he was heterozygous (trait)?
Heterozygous trait generally have milder form, so they don’t require frequent blood transfusions.
So they are immunologically less risk than sickle cell disease. Studies have shown to have similar graft and patient survival as in sickle cell disease
Okafor UH, Aneke E. Outcome and challenges of kidney transplant in patients with sickle cell disease. Journal of transplantation. 2013 Jan 1;2013.
Nath J, McDaid J, Bentall A, Ball S, Ready AR, Inston NG. Sickle Cell and Renal Transplant: A National Survey and. children. 1997;1992:4.
Igbokwe M, Olatise O, Faponle A, Aremu A, Revanur V, Jiwoh H, Obajolowo O, Ameh I. Kidney transplantation in sickle cell disease patients: Case series and experience from a Nigerian kidney transplant center. Indian Journal of Nephrology. 2022 Mar;32(2):164.
thanks, prof Ahmed for interesting explanation
Outcome of Transplantation in sickle cell disease:
The overall survival rate of transplant is better than on dialysis for sickle cell disease patients… 2000-2019 UNIS database demonstrates that sickle cell disease patients had higher mortality of graft failure compared to the control group, but not with dialysis…. later many studies have reported increased survival rate of Sickle cell disease patients on transplant with improved outcomes in the recent years…
Management of this patient:
The patient has a high risk of sickle cell crisis due to previous history and surgery for the transplant may precipitate one…The aims are to optimize volume status, prevent infections, prevent sickle cell crisis, correction of anemia and VTE prophylaxis
Immunization is essential before surgery to prevent infections as most vaccines cant be given after transplant… In view of multiple blood transfusion it is essential to be vigilant about HLA antibodies and attention to desensitization is needed before transplant
.
Anemia management
There are no guidelines to recommend Hb transfusion at one level…. Those patients who have recurrent vaso occlusive episodes it is recommended to maintain the hemoglobin to only 8-10 gm%. This is to avoid hyperviscosity triggering crisis…This is usually when the Hb electrophoresis reveals HbS to be more than 35% of the hemoglobin…
IV iron is not recommended as these patients already have iron overload….
In those patients with sickle cell disease there is a greater likelihood of metabolic acidosis and hyperkalemia, hence balanced solutions should be used for fluid replacement….
Due to hyperviscosity these patients will have to be on anticoagulation..
Hydroxyurea is the primary medication that is utilized in the treatment of SCD especially in those with repeated vasoocclusive episodes…
The immunosuppression:
As mentioned earlier, there is greater risk of infection as compared to normal transplants due ti SCD. The choice of the donor should be correct as it is better to avoid HLA incomaptible and ABOi donors due to more immunosuppressive requirement… The maintanence of normal hemoglobin, preserving the oxygenated hemoglobin and elevation of fetal hemoglobin by use of the hydroxyurea is recommended in all patients…mTOR inhibitors which affect cellular development has shown to be improving status of fetal hemoglobin….they can be added to the immunosuppresive drugs
The risk is more in this patient as he is a homozygous trait requiring more blood transfusion and more sensitization….he has SCD…Whereas Sickle cell trait is related to single mutated gene requiring less transfusion and maintains normal hemoglobin..The survival of sickle cell trait is near normal to normal individuals
What is the outcome of kidney transplantation in sickle cell disease?
Sickle cell disease is the most inheritable blood disease in the United States.
Sickle cell does affect the kidney. It is firstly manifested by macroalbuminuria in early childhood, then it progress to chronic kidney disease and renal failure in half of the patients with HbSS genotype. ESRD occurs in 5% up to 18% with a median age of 23 years. However, only of those patients receive kidney transplant. Patient and allograft survival in SCD kidney recipients are worse than other diagnoses. However, survival is better than being on dialysis.
How do you manage his transplantation (pre, intra and postoperative)?
Preoperative:
Vaccination against capsulated organisms i.e., strept pneumonia, nissria and Hemophilus influenza
Done 2 weeks before transplant due to hyposplenism which may complicate sickle cell disease.
Maintain hgb level around 10 gram/ dl and hgS level less than 30% by frequent blood transfusion or exchange transfusion.
Immunological risk assessment should be done carefully, as they are transfusion dependent . so done after the last blood transfusion by 3 months.
Intraoperative: good hydration to avoid sickling, avoid major bleeding and excessive blood transfusion causing hemoconcentration.
Postoperative:
Good analgesia and maintain Hgb level
Discuss immunosuppression?
Being frequent blood transfusers, they would have high cRF and being more sensitizied. So, antibody dependent induction is necessary and maintenance with triple immunosuppressive drugs
Would it be different if he was heterozygous (trait)?
Trait patients are less manifested and less transfusers, so less liable for CKD and for sensitization
1）What is the outcome of kidney transplantation in sickle cell disease?
Kidney transplantation can be successful in recipients with sickle cell disease/trait. Complications are common, including infection and sickle cell crisis. Appropriate immunosuppression is essential, as the group remains at risk for allograft rejection, as well as serious infections.
2）How do you manage his transplantation (pre, intra and postoperative)?
Pre transplant
a)Counsel the benefits and possible complications of renal transplant in SCD / trait recipient.
b) Psychiatry assessment for suitability for kidney transplat.
c)Exclude active infection, malignancy, specifically disease activity for SCD in this patient,
d) Multidisciplinary input regarding the benefits and risks to proceed for renal transplant ( Transplant Nephrologist, Transplant surgeon, Anesthesiologist, Hematologist. Cardiologist, Pulmonologist )
e)ensure complete vaccination . COVID 19, pneumococcal, meninggococal.
Intro Operative
a) Short ischemic time.
b) Minimizing blood loss.
c) close vital signs monitoring.
d) antibiotic prophylaxis.
Post operative
a)Analgesia
b)Infection control.
c) Surveillance for acute graft rejection
3）Discuss immunosuppression?
Desensitization ATG
Maintenance : Tac + steroid + MMF ( may substitute with hydroxyurea )
4）Would it be different if he was heterozygous (trait)?
less severe anaemia. reduce complications of renal transplant.
What is the outcome of kidney transplantation in sickle cell disease?
Patients with SCD who underwent kidney transplant has better survival rates compared to patients on dialysis these days .Previously in 2000-2019 UNOS/OPTN database ,graft failure and mortality was more in recipients and considered contraindication but now literature review revealed patient survival of 87% at one year and graft survival 67% at one year. Another study mentioned 56% -10 year survival rate.
How do you manage his transplantation (pre, intra and postoperative)?
Management of renal transplantation involved multidisciplinary team including hematologist, Renal transplant physician ,cardiologist and renal transplant surgeon. Detailed cardiac evaluation needed before transplant to rule out pulmonary hypertension and also need to vaccinate the patient because of auto-splenectomy. Good HLA match without DSA and ABO antibodies Avoidance of all precipitating risk factors like acidosis ,dehydration etc.Hemoglobin should be maintained around 10g/dl before transplant and special precaution during surgery in regard to fluid should be done i.e., warm fluids preferred as hypothermia also a risk factor. Close monitoring of I/V fluids post-operatively guided by CVP and urine output to avoid dehydration. Pain should be controlled with adequate analgesics.All symptomatic patients should be on Hydoxyurea and it should be started at least 02 months before transplantation.
Immunosuppression:
Maintenance immunosuppression will remain the same as in other patients and include tacrolimus, mycophendlate and prednisolone ,however, induction to be done with ATG as chances of allo- sensentisatiion due to blood transfusion are high.
Would it be different if he was heterozygous (trait)?
Immunological risk is less in such patients ,also complication like crisis and infection rate is less so patients can be transplanted with less immunosuppression and patient and graft survival is similar to sickle cell patients.
REFERENCE:
U H Okafor, E Aneke. Outcome and challenges of kidney transplant in patients with sickle cell disease. J Transplant. 2013;2013:614610
KDIGO recommend not excluding candidates with sickle cell disease from kidney transplantation in the absence of active, severe extrarenal sickle cell disease
The recommendations for perioperative
management of kidney transplant in patients with SCD to enhance better outcome
include the following:
(i)Ensure the operating and anesthesia teams
are aware of the diagnosis of a sickle cell syndrome and the need for special
attention in the patient.
(ii)Ensure that patients preoperative
haemoglobin of 10 g/dL is achieved.
(iii)Reduce hyperviscosity especially in
patients with SCD-SC; there may be a need for exchanging blood transfusion.
(iv)Minimize alloimmunization by giving
antigen-matched blood.
(v)Preoperative monitoring of intake and
output, hematocrit, peripheral perfusion, and oxygenation status.
(vi)Intraoperative monitoring of blood
pressure, cardiac rhythm and rate, and oxygenation.
(vii)Intensive postoperative care including
attention to hydration, oxygen administration with careful monitoring, and
respiratory therapy.
(viii) Scrupulous followup of patients with
stringent monitoring of patients wellbeing, renal function, drug level, and so
forth.
Discuss immunosuppression?
Recurrent blood transfusion raised the possibility of being highly sensitized.
And need for heavy immunosuppression +/- sensitization
Would
it be different if he was heterozygous (trait)?
sickle cell trait lesser degree of
complication than SCD but higher to the general population
KDIGO Clinical Practice Guideline on the
Evaluation and Management of Candidates for Kidney Transplantation 2020
Okafor UH, Aneke E. Outcome and challenges
of kidney transplant in patients with sickle cell disease. J Transplant. 2013;
614610.
1.What is the outcome of kidney transplantation in sickle cell disease
The outcome of kidney transplant in SCD patients is variable,Earlier studies on kidney transplant in SCD patients suggested poor allograft survival and other disease-specific problems.However, later studies have reported graft and patient survival rates comparable to those of nondiabetic patients with normal haemoglobin genotype.
A more recent study of renal transplantation in SCD reported short-term patient and allograft outcomes comparable to other age-matched African Americans.
There was a trend toward improved survival in those SCD patients who received transplants compared to those on chronic dialysis with one-year patient and graft survival of 87% and 67%, respectively.
2.How do you manage his transplantation
Pre-operative
Donor selection is also a very important key factor. Genotypes of all potential donors are requested and anyone with the abnormal sickle cell gene is excluded with AA donors favored.
They would have had multiple blood transfusions necessitating the need for desensitization prior to transplant , if they are highly sensitized.
Hyposplenism from autosplenetomy, vaccinations against S. pneumoniae, N. meningitidis, H. influenza type b, and influenza virus are strongly recommended at least 2 weeks before transplant surgery.
Gradual correction of anemia by erythropoietin stimulation can be commenced months prior to surgery in order to limit the need for blood transfusions.
use of hydroxyurea in these patients pre and postoperatively has been shown to reduce incidents of crisis, acute chest syndrome, and mortality by up to 40%.
Intra-operative
A wide bore central line for hydration, arterial line for blood gas monitoring, and general anesthesia with good oxygenation . Surgically, gentle dissection, meticulous hemostasis, and short warm and cold ischemic time enabled early graft function
Post-operative
In the immediate postoperative period, liberal morphine-based patient-controlled analgesia was ensured to avoid pain-induced crisis.
oral hydroxyurea coupled with the immunosuppressants, antimalarial prophylaxis, co-trimoxazole for 6 months, prednisolone , atorvastatin daily rabeprazole daily, valganciclovir for 6 months, tuberculosis prophylaxis for 3 months, antifungal prophylaxis for 3 months, liberal fluid intake, and regular clinic visits.
3.Discuss immunosupression
They need frequent blood transfusion, so they are sensitized due to prior blood transfusion.
ATG for induction
Triple therapy ( steroid,MMF,Tac)
If he was heterozygous
No blood transfusion, No desensitization
Igbokwe M, Olatise O, Faponle A, Kidney Transplantation in Sickle Cell Disease Patients: Case Series and Experience from a Nigerian Kidney Transplant Center. Indian J Nephrol. 2022 Mar-Apr;32(2):164-167.
What is the outcome of kidney transplantation in sickle cell disease?
In spite of graft survival is lower in sickle cell disease but still not contraindicated to transplantation and better survival than continuing on dialysis.
How do you manage his transplantation?
Pre operative:
– Vaccinations as H influenza, S. Pneumoniae, and N meningitidis for hyposplenism or auto splenectomy
– correction of anaemia by erythropoietin but takes long time and target hemoglobin is 10
Or blood transfusion in urgent situations can use blood transfusion and transplant should be delayed for at least 3 months.
– use of hydroxyurea as it reduces HB S and reduces crisis.
Intraoperative:
Good hydration and frequent monitoring of blood gases and avoid hypoxia and acidosis
Gentle handling in surgery
Short ischemia time
Post operative:
ICU admission with frequent monitoring of hydration, blood pressure , blood gases
Pain management
Hydroxyurea
Cotrimoxazole and valganciclovir for 6 months
Discuss immunosuppression?
Due to frequent blood transfusion, so it is considered high risk and need induction with ATG and triple immunosuppressive.
Outcome of kidney transplantation in sickle cell disease:
There are variable reports of graft and patient survival after transplant in sickle cell disease versus non-diabetic normal genotype hemoglobin.(1) A few recent studies show short-term graft and patient survival similar to that of normal hemoglobin genotype patients. Long-term graft survival is lower than in normal hemoglobin recipients, but overall morbidity and mortality are better than on long-term dialysis.(1) Whenever donor is available and if condition permits, transplant is best option than to be on dialysis even in sickle cell disease patients. Table 1 shows the outcomes of transplant in sickle cell disease in various studies. (1)
Pre-operative management:
Intraoperative management:
Postoperative management:
Immunossuppression:
Would it be different if he was heterozygous (a trait)?
Sickle cell trait has less susceptibility to crises unless there is dehydration or sepsis. They don’t need exchange transfusions, hydroxyurea and need standard triple drug immunosuppression.
Reference:
What is the outcome of kidney transplantation in sickle cell disease?
Patients with sickle cell disease are liable to develop sickle cell nephropathy which may develop end-stage renal disease that can be treated via dialysis or renal transplantation.
Premature death is 7-fold higher in SCD-ESRD on dialysis compared to non-SCD-ESRD on dialysis.
SCD renal transplant recipients are liable to more sensitization because of repeated blood transfusion, development of de-novo DSA, cardiomyopathy related to secondary hemochromatosis.
Graft and patient survival outcomes are lower in SCD renal transplant recipients compared to non SCD recipients. However, transplantation is a better treatment option than being on dialysis.
Pre-transplantation counselling is important beforehand to discuss risks like alloimmunization and chance of developing de-novo DSA and chronic rejection from sepsis.
How do you manage his transplantation (pre, intra and postoperative)?
1- Blood transfusion aiming hemoglobin level above 90 g/L, HBSS below 30. if HB below 100g/L, or 2 gm/L below the patient’s baseline associated with symptomatic anaemia–à> simple transfusion using antigen matched blood (Rh and K to minimize the risk for allo-immunization. If HB>100 g/L—à exchange transfusion, and if it is not available, remove 10 ml/Kg blood and replaced by 5 ml/kg of PRBCs. Hb above 100 g/L will increase blood viscosity and increase risk of thrombosis.
2- Monitor of iron profile and ferritin because of high risk of secondary hemochromatosis and need for iron chelating agents.
3- Anesthesia clearance.
4- Adequate Hydration by balanced solutions.
5- Adequate analgesia and pain control.
6- Thromboprophylaxis.
7- Monitoring of vital signs and maintain stable hemodynamics.
8- Antibiotic, antiviral prophylaxis to avoid sepsis.
9- Complete Vaccination before transplantation: pneumococcal and meningococcal vaccines.
Discuss immunosuppression?
After assessment of sensitization, and immunological risks, desensitization should be considered if needed before transplantation.
Induction IS will be decided according to immunological risk, maintenance IS will be triple IS (CNI, MMF, and steroids).
Hydroxyurea is an antimetabolite medication that is used to increase the of Hb F instead of Hb S. it is usually used in SCD patients to lower the incidence of vaso-occulsive crisis, acute chest syndrome, hyperfiltration, and micro-albuminuria.
Use of hydroxyrea after kidney transplantation in SCD patients’ needs further studies especially it can interact with MMF and Azathioprine and might increase the risk of more bone marrow suppression.
Would it be different if he was heterozygous (trait)?
Heterozygous (trait) Hb Ss is associated with less sensitization, less infection, and less vaso-occlusive crisis that will make the patient more surgically fit.
What is the outcome of kidney transplantation in sickle cell disease?
One year and five years graft survival is lower than non SCD patients
One year and five year patient survival are similar between SCD and non SCD patients.
How do you manage his transplantation (pre, intra and postoperative)?
Pre operation:
pre transplantation assessment of the the recipient with SCD including cardiology and pulmonary assessment. Correction of anemia by ESAs and blood transfusion, exchange transfusion may be need to normalize Hbs , vaccination against N.meningitides, H.infuenza and S.pneumonia at least 2 weeks before transplantation. Genetic testing for the prospective donor if he is relative to the recipient. As the patient is highly sensitized due to multiple blood transfusion, desensitization must be done .
Intra operation:
Adequate hydration and antibiotics with optimal analgesia and blood transfusion.shorten warm and cold ischemia time with delicate surgical approach.
postoperative period:
Morphine based analgesia to decrease the incidence of pain induced crises , good cover AB and prevent septic events, prophylactic Ab like co-trimoxazole antiviral and antifungal agents.
Discuss immunosuppression?
Desensitization and ATG or Alemtuzumab
Triple maintenance IS
Would it be different if he was heterozygous (trait)?
No need for desensitization as there is no history of repeated blood transfusion.
What is the outcome of kidney transplantation in sickle cell disease?
Although survival improves after transplantation in SCD patients,
USRDS and UNOS databases revealed that kidney transplant recipients with SCD had reduced allograft and patient survival compared to non-SCD kidney transplant recipients
higher risk of losing graft in SCD kidney transplant recipients is multifactorial :
– due to vaso-occlusion resulting in kidney infarction, papillary necrosis, hematuria, FSGS, and diabetes insipidus
-also iron and heme deposition in proximal renal tubules and acute tubular injury was evident in biopsies.
– Chronic allograft injury and anemia can worsen kidney function .
– Allograft thrombosis in sickle cell crisis can occur.
How do you manage his transplantation (pre, intra and postoperative)?
-This patient mostly of high immunological risk due to repeated blood transfusion prober selection of matched donor to decrease the risk of rejection is important, desensitization and induction with ATG will improve graft survival .
-Vaccination against encapsulated organism before surgery for cases with auto spleen-ectomy.
– adequate dialysis.
– correction of anemia with erythropioten to decrease the need for blood transfusion and keep HBS below 30%.
– Hydroxyurea which acts to increase levels of HB F to dilute the levels of Hb S and reduce risk of polymerization and blood transfusion have been the primary methods used to treat SCD complications .
-multicenter study on 34 SCD kidney transplant recipients between 1997 and 2017 ensured the safety of long-term automated exchange blood transfusions (EBT) with improvement in allograft and patient outcomes and no increase in antibody formation or allograft rejection.
intra-operative:
during surgery its recommended to decrease blood loss ,
gentle surgical procedure ,good hydration, analgesia, monitor HB level, decrease cold and warm ischemia time .
In the Postoperative period
-strong analgesia to avoid precipitation of sickling crisis.
– Prophylactic anticoagulant therapy.
– prophylactic antibiotics to prevent infection, with follow up sepsis markers , CRP, TLC, temperature .
-pneumococcal and meningococcal vaccines, prophylaxis for CMV ,TB and ,fungal infections.
– Hemoglobin electrophoresis to determine HBS level.
Discuss immunosuppression?
This patient is high risk patient due to previous sensitization so ATG is preferred for induction
Maintenance on triple immunosuppression although will give better graft survival but may increase the risk of infection
Hydroxyurea can be used although data on the effects of hydroxyurea on kidney transplant allograft are limited, the use of hydroxyurea has shown potential benefits in reduction of proteinuria, stabilization in kidney function, and reduced mortality risk among non-kidney transplant SCD patients.
· Would it be different if he was heterozygous (trait)?
Yes heterozygous sickle cell trait patients aren’t at the same risk of repeated blood transfusions so less risk of sanitization.
They also have less risk of thrombosis , infections.
But still need close monitoring of HBs level by electrophoresis, prophylaxis against infection.
reference
Leeaphorn N, Thongprayoon C, Vaitla P, Hansrivijit P, Jadlowiec CC, Mao SA, Chewcharat A, Katari S, Pattharanitima P, Boonpheng B, Kaewput W, Mao MA, Cooper M, Cheungpasitporn W. Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000-2019 UNOS/OPTN Database. J Clin Med. 2021 Jul 11;10(14):3063.
Kidney transplantation in sickle cell nephropathy (SCN) patients
with ESKD has the best outcome compared with those who did
not receive KT (10-year survival of 56% vs 14%).
This outcome is improving nowadays and is increasing to 70%.
On year graft survival is about 67-82%. SCN may occur in
transplanted kidney unless HSCT is done.
These patients must receive vaccines against H. influenza, pneumococcus and meningococcal. Booster of
vaccines would be needed before transplantation.
Perioperative hemoglobin level should be 10g/dL and Hb S should be less than 30%. It is better to use exchange transfusion by using antigen-matched blood to avoid hyper-viscosity.
They need close attention for hydration, oxygenation and pain
control.
They are at risk of venous thromboembolic evevnts that should be
considered.
In the case of need for erythropoiesis-stimulating agents (ESA), epoetin or darbopoetin would be used with caution to avoid hyper-viscosity and its complication (vaso-occlusion, stroke, VTE) by rapid rising of Hb more than 10 g/dL.
We should avoid iron overload and if detected, iron chelation
therapy is indicated.
Supplemented iron is prescribed only for the treatment of iron
deficiency.
They should receive hydroxy urea to increase Hb F two months
before transplantation.
These patients are highly sensitized due to repeated blood
transfusions.
So induction therapy depends on immunological risk.
Steroid should be used with caution because of high risk for
avascular necrosis of hip.
SCT patients have usually milder disease but they have high
risk of medullary carcinoma of kidney that needs evaluation.
They should be monitored for UTI and thrombosis, too.
Reference:
Up to date
The kidney transplantation still carries best option for sickle cell anemia patient than waiting on dialysis. Although, death censored graft survival is inferior to those without sickle cell anemia.
Pre-operative:
Hgb should be kept not more than 10 g/dl to decrease blood viscosity. This done by either blood transfusion (better to be antigen –matched) or exchange transfusion.
Hgb electrophoresis to keep Hgb S < 30%
Vaccination (pnumococcal and meningococcal vaccine)
My start hydroxyurea if not on already
Intraoperative
Discuss the case with anaesthesia
Close monitoring of the patient
Good hydration
careful donor selecton
Post-operative
ICU
Antibiotics prophylactic
analgesia
Hydration
Monitoring
Immunosuppression:
ATG induction
hydroxyurea which is used in the treatment of SCD as it increases HB f leve so prevent sickling (vaso-oclusive crisis) may be used instead of azathioprine although no data support it.
Monitor of DSA post-transplant (recurrent blood transfusion increased risk of rejection)
if patient is heterozygote
no difference
the outcome of kidney transplantation in sickle cell disease for patients and allograft was worse than recipient with another diagnosis but more studies are needed.
intravenous fluid and analgesia
What is the outcome of kidney transplantation in sickle cell disease?
Recent studies suggest graft and patient survival rates comparable to those of nondiabetic patients with normal haemoglobin. Recent data showed that exchange blood transfusion post renal transplant is effective and safe, leading to better graft and patient outcomes and no increase in antibody formation or graft rejection. Some evidences suggest that treatment with exchange blood transfusion aimed at keeping the HbS level <30% reduces graft loss and improves patient survival post-kidney transplantation.
How do you manage his transplantation (pre, intra and postoperative)?
Patients with SCD are prone to develop various organ dysfunctions eg. cardiovascular, pulmonary, and immunologic complications. These complications influence patients over all outcome.
Pre operative preparation:
– Selection of compatible nd suitable recipient and donor.
– Pre-operative preparation including: adequate dialysis, exchange transfusion and correction of anaemia.
– Maintain HbS< 30% with exchange transfusion.
– Hydroxycarbamide: start two months before trnsplnt.
– Vaccination: pneumococcal and meningococcal
-Maintenance of appropriate hydration and oxygenation
Intra operative preparation:
– Maintenance of appropriate hydration and oxygenation.
– Monitoring of temperature, BP, electrocardiographic features, and oxygenation.
– Maintaining Hb level >9 g/dl.
– Effective anesthesia and analgesia.
Post operative preparation:
– Again attention to hydration and oxygenation.
– Attention to post-operative respiratory care.
– Effective analgesia and pain relief therapy.
– Anticoagulant therapy.
Discuss immunosuppression?
– Induction: according to the baseline DSA level and sensitization. Basiliximab, ATG or Alemtuzumab may be selected.
– Maintenance: combination of CNI, MMF and Prednisolone.
Would it be different if he was heterozygous (trait)?
Heterozygous patients are less likely to have severe anaemia.
This patient is sicker and looking for RTX and came with frequent crises
first: we need to know the cut-off limit of Hb, which requires it to go through the whole transplant operation
This patient’s HbS should be less than 30% to deliver good o2 to the tissue
. Usually, we need a blood transfusion in case of vast occlusive disease. Blood transfusions will improve O2 delivery to the tissue but, at the same time, will increase the basso occlusive problems.
usually;
prefer to go for WBCS-depleted blood transfusion to reduce the sensitisation and alloimmunity.
Perioperative preparation:
What are the specific vaccines to be taken?
What is the management of an SC crisis in a transplant patient?
The dose do we need to put the transplant recipient of hydroxyurea?
Yes, all SCD recipients should be started on hydroxy urea two months before transplant to increase HBV and reduce sickling.
references
update
This patient is sicker and looking for RTX and came with frequent crises
first: we need to know the cut-off limit of Hb which needs it to go through the whole transplant operation
This patient’s HbS should be less than 30% to deliver good o2 to the tissue
usually, we need a blood transfusion in case of vast occlusive disease. Blood transfusions will improve O2 delivery to the tissue but at the same time will increase the basso occlusive problems.
usually;
prefer to go for WBCS depleted blood transfusion to reduce the sensitization andalloimmunity.
Perioperative preparation:
What are the specific vaccines to be taken?
What is the management of a SC crisis in a transplant patient?
Dose we need to put the the transplant recipient of hydroxy urea ?
yes all SCD reciepent should be started on hydroxy urea 2 month before transplant to increase HBf and reduce sickling
referrencs
uptodate
According to literature patient survival of these patients is better with transplantation rather then hemodialysis.
SCD is not contraindicated for transplantation, however, the pre, peri and post operative complications can be minimized by good hydration, pre-transplantation vaccination, good Hb level, minimal sickling cells by apheresis/ exchange. Can be given hydroxyurea weeks 4 weeks transplantation.
1- In an analysis of Leeaphorn et al, SCD (sickle cell disease) was significantly associated with lower patient survival (HR 2.87; 95% CI 1.75–4.68) and death-censored graft survival (HR 1.98; 95% CI 1.30–3.01), compared to non-SCD recipients. Patient and allograft survival in SCD kidney recipients was worse than recipients with other diagnoses such as diabetes, glomerular disease, and hypertension as the cause of end-stage kidney disease.
2- Sickle cell cases are highly sensitized as they have multiple blood transfusions and recurrent vaso-occlusive crises.
Igbokwe M, reported 3 cases of successful transplant Kidney transplantation in Nigeria. Generally, there is a need for appropriate donor and recipient selection, proper preoperative preparation regarding the correction of chronic anaemia (preoperative exchange blood transfusion), and adequate haemodialysis and plasmapheresis to optimize these patients for surgery. Moreover, they required preoperative vaccination against encapsulated organisms due to autosplenectomy.
Adequate hydration Intra and postop should be given, and strong analgesics (with avoidance of NSAIDs) should be prescribed. Intra-op vitals, oxygen monitoring and perfusion should be observed carefully.
3- Since these patients are highly sensitised, Antithymocyte globulin can be used unless contraindicated. In such cases, Basiliximab or Alemtuzumab can be used. Standard maintenance therapy will consist of CNI (tacrolimus), MMF and steroids.
4- heterozygous (trait) doesn’t require frequent blood transfusion hence he will not be highly sensitised and will need desensitization therapy.
References:
1- Leeaphorn N, Thongprayoon C, Vaitla P, Hansrivijit P, Jadlowiec CC, Mao SA, Chewcharat A, Katari S, Pattharanitima P, Boonpheng B, Kaewput W, Mao MA, Cooper M, Cheungpasitporn W. Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000-2019 UNOS/OPTN Database. J Clin Med. 2021 Jul 11;10(14):3063. doi: 10.3390/jcm10143063. PMID: 34300230; PMCID: PMC8305507.
2- Igbokwe M, Olatise O, Faponle A, Aremu A, Revanur V, Jiwoh H, Obajolowo O, Ameh I. Kidney Transplantation in Sickle Cell Disease Patients: Case Series and Experience from a Nigerian Kidney Transplant Center. Indian J Nephrol. 2022 Mar-Apr;32(2):164-167. doi: 10.4103/ijn.IJN_28_20. Epub 2022 Mar 9. PMID: 35603115; PMCID: PMC9121718.
Compared to SCD patients on maintenance dialysis, the survival rate of people with SCD who have had a kidney transplant is higher. An analysis of the 2000–2019 UNOS/OPTN Database demonstrated that SCD recipients have a higher probability of graft failure and mortality compared to the control group.
Hematologist and cardiac/respiratory evaluations are required before surgery. SCD patients with increased TRJV and probable pulmonary hypertension may benefit from ECHO, 6-minute walk distance, and/or NT-BNP. A thorough PFT should encompass spirometry, diffusion capacity, lung volumes, sleep-disordered breathing screening, albuminuria treatment, blood pressure control, and VTE management.
Renal Doppler ultrasonography and imaging for the assessment of papillary necrosis
Transesophageal ultrasonography can be used to preserve euvolemia and adequate oxygenation intraoperatively.
Post-op hydration, O2 treatment, pain control, anticoagulation to prevent venous thromboembolism, and prophylactic antibiotics are recommended.
Sling graft surgery is suggested as follows:
1. Preoperative transfusions until HbS is below 30%
2. Postoperative recipient preoxygenation with 40% O2 lasted 48 hours.
3. The renal artery and gonadal vein are supplied with 37°C saline before the arterial anastomosis. After warming the vented solution, the arterial anastomosis is completed, 200 mL of recipient blood is vented and discarded, and the gonadal vein is ligated.
4. Postoperative surgical, nephrology, and hematological input is needed.
5. Immunosuppression with tacrolimus, mycophenolate mofetil, prednisolone, and basiliximab
Multiple blood transfusions have rendered these patients extremely sensitive. ATG induction should be accompanied by triple immunosuppressant maintenance. MMF can be replaced with hydroxyurea, which has the added benefit of raising HbF. Reduce steroids gradually to reduce hip avascular necrosis incidence.
Heterozygous sickle cell trait recipients do not require frequent blood transfusions and have a decreased risk of complications compared to sickle cell disease patients. These instances pose a lower immunological risk and may not require desensitization.
The outcome of kidney transplant in these SCD patients is variable. Earlier reports on kidney transplant in SCD patients suggested poor allograft survival and other disease-specific problems. However, later studies have reported graft and patient survival rates comparable to those of nondiabetic patients with normal haemoglobin genotype. A more recent study of renal transplantation in SCD reported short-term patient and allograft outcomes comparable to other age-matched African Americans.
Recent data showed that EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection. There is some evidence that treatment with regular exchange blood transfusion (EBT) aimed at keeping the HbS level <30% reduces graft loss and improves patient survival post-kidney transplantation without increasing the risk of graft rejection or HLA sensitization.
Patients with SCD are prone to various organ dysfunctions which predispose them to haematologic, cardiovascular, pulmonary, and immunologic complications. These complications influence and compromise the choice, fitness, and outcome of kidney transplants in these patients. This clinical sequel could manifest during pre, intra- and postoperative management of these patients.
The recommendations for perioperative management of kidney transplant in patients with SCD to enhance better outcomes include the following:
Therapeutic immunosuppression is a cardinal component of the management of kidney transplants; this, however, poses a potential challenge in curtailing infection in SCD patients following a kidney transplant. However, adequate prophylactic measures, including the use of appropriate pre- and postexposure vaccination, antibiotics, and strict safety precautions, had been associated with optimal control of infection in these patients. Further measures in the control of infection in these patients include barrier nursing, intensive post-op management, strictly personal and environmental hygiene, drug monitoring, surveillance and screening for culprit infections and malignancies, early therapeutic interventions, and infection control.
Heterozygous patients are less likely to have anaemia, so the risk associated with blood transfusion is less likely in these patients.
References:
Reference:
Joanna C. Willis, et al: outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion; PLoS One. 2020; 15(8): e0236998.
Published online 2020 Aug 13. doi: 10.1371/journal.pone.0236998
What is the outcome of kidney transplantation in sickle cell disease?
· A five-year study of patients with SCD receiving hemodialysis in France reported a 7-fold increase in the risk of death for these patients compared to patients without SCD, and a much lower incidence of renal transplantation (26 vs 54%), thought to be due to a combination of poorer cardiovascular fitness, ethnicity and sensitization1.
· The long-term graft and patient survival in SCD are inferior compared to patients with other causes of ESRD, the prognosis is far better after transplantation compared to receiving dialysis and is now similar to that of patients with diabetes2.
· Transplant surgery on severely anemic patients with a high percentage of sickle hemoglobin is high risk, potentially triggering life- and allograft-threatening vaso-occlusive complications, with an increased risk of delayed graft function or primary non-function3.
· In a retrospective study by Willis JC et al; 1, 5- and 10-year patient survival was 91%, 72% and 33% respectively, with death- censored graft survival at 87%, 61% and 19%3.
· The overall incidence of biopsy-proven rejection was 38%3.
· Patient survival, death censored graft survival and graft function (as estimated by MDRD eGFR) were superior at all time-points post-transplant in those on an EBT program compared to those not on an EBT program3.
· Graft survival and function were superior in SCD patients receiving EBT, with lower rates of SCN recurrence in the graft and no increase in HLA sensitization, DSA formation or rejection, despite an increased transfusion burden3.
· Acute vaso-occlusive crises (VOC) are reported as rare in patients receiving dialysis but the frequency increases post renal transplantation, possibly due to a rise in endogenous erythropoietin release3.
How do you manage his transplantation (pre, intra and postoperative)?
Pre-op preparation:
· MDT including hematologist.
· Appropriate and optimal selection of a suitable recipient and matching donor with better HLA compatibility.
· Appropriate pre-operative preparation including: adequate dialysis, plasmapheresis(if needed) and correction of anaemia.
· Maintaining Hb >90g/l and HbS< 30%, preferably via exchange transfusion.
· Hydroxycarbamide (HC, also known as hydroxyurea) is a cytotoxic, antimetabolite approved for use in SCD. Although it has pleotropic effects, it primarily acts to increase levels of fetal haemoglobin which dilute the levels of HbS and reduce risk of polymerization. Clinical benefits include lower rates of pain, acute chest syndrome and need for blood transfusion. HC can be used with dose reduction according to eGFR.
· Attention to hydration and oxygenation
Intra-op preparation:
· Selection of less aggressive or extensive surgical procedure.
· Attention to hydration and oxygenation.
· Monitoring of temperature, BP, electrocardiographic features, and oxygenation.
· Maintaining Hb level >9 g/dl.
· Effective analgesia and pain relief therapy.
Post-op preparation:
· Attention to hydration and oxygenation.
· Attention to post-operative respiratory care.
· Effective analgesia and pain relief therapy.
· Prophylactic anticoagulant therapy.
· Vaccination: pneumococcal and meningococcal vaccines beside H.influenzae type B.
· Prophylaxis therapy for CMV and PJP. Anti-TB prophylaxis and antifungal prophylaxis if at risk.
Discuss immunosuppression?
· For induction: according to the baseline DSA level and sensitization. Basiliximab, ATG orAlemtuzumab may be selected.
· For maintenance IS: CNI, MMF and Prednisone.
Would it be different if he was heterozygous (trait)?
It will be different, as sickle cell trait are less likely to require blood transfusion and hence the consequent complications in regard to BT.
References:
1. Nielsen L, Canoui-Poitrine F, Jais JP, Dahmane D, Bartolucci P, Bentaarit B, et al. Morbidity and mortal- ity of sickle cell disease patients starting intermittent haemodialysis: a comparative cohort study with non- Sickle dialysis patients. Br J Haematol. 2016; 174: 148–152. https://doi.org/10.1111/bjh.14040 PMID: 26992059
2. Gerardin C, Moktefi A, Couchoud C, Duquesne A, Ouali N, Gataut P, et al. Survival and specific out- come of sickle cell disease patients after renal transplantation. Br J Haematol. 2019; 187: 676–680. https://doi.org/10.1111/bjh.16113 PMID: 31348518
3. Willis JC, Awogbade M, Howard J, Breen C, Abbas A, Harber M, et al. (2020) Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion. PLoS ONE 15(8): e0236998. https://doi.org/10.1371/journal. pone.0236998
· What is the outcome of kidney transplantation in sickle cell disease?
Although survival improves after transplantation in SCD patients , worse outcomes among them remains a concern compared to non-SCD recipients.
USRDS and UNOS databases revealed that kidney transplant recipients with SCD had reduced allograft and patient survival compared to non-SCD kidney transplant recipients
The allograft loss high risk in SCD kidney transplant recipients is multifactorial due to vaso-occlusion resulting in kidney infarction, papillary necrosis, heamaturia, FSGS, and diabetes insipidus
iron/heme deposition in proximal renal tubules and acute tubular injury in biopsies.
Chronic allograft injury and anemia can worsen kidney function .
Allograft thrombosis in sickle cell crisis can occur.
· How do you manage his transplantation (pre, intra and postoperative).?
Donor selection is difficult due to limited living donors pools and limited spaces for KT in SCD patients who require highly specialized care
All potential donors genotypes particularly in sibling are needed to exclude those with sickle cell gene.
The patient has immunological risk due to blood transfusion so desensitisation will be needed.
Early post-transplant blood transfusion can increase immunological risk and rejection risk meanwhile a recent study published that blood transfusion with adequate immunosuppressive regimens within 1 week post-kidney transplantation is safe without significant increase of de novo HLA-DSA development
Another study declared the benefit of long-term automated exchange blood transfusions (EBT) with enhancement in allograft and patient outcomes without increase in antibody formation or allograft rejection
Vaccination against encapsulated organism can be done 4 weeks before surgery for cases with autospleenectomy
Erthyropoietin can be given prior transplantation to decrease the need for blood transfusion
If blood transfusion is needed , 3 months delay will be better and repeat the cross-matches to exclude the presence of new antibodies or plasma exchange.
Patient must be well hydrated with , adequate analgesia, antimalarials, antibiotic therapies, and thromboprophylaxis are mandatory
Hydroxyurea pre and postoperatively use can decrease proteinuria, stabilization in kidney function, and reduced mortality risk among non-kidney transplant SCD patients
Surgically, gentle dissection, careful hemostasis, and short warm and cold ischemic time can ensure early graft function.
Post operative period oral hydroxyurea with the immunosuppressants, due to sickle crisis risk
Those patients are at high risk of sepsis therefore antimalarial prophylaxis, co-trimoxazole for 6 months, statins,PPI, valganciclovir for 6 months, tuberculosis prophylaxis for 3 months, antifungal prophylaxis for 3 months, with regular follow up are crucial
· Discuss immunosuppression?
ATG can be used as induction
Maintenance ;tacrolimus, mycophenolate mofetil, prednisolone,hydroxyurea ,folic acid , vitamin c
· Would it be different if he was heterozygous (trait)?
Yes heterozygous sickle cell trait donot need multiple blood transfusions and are at lower risk of complications compared to those with sickle cell disease
Those cases have less immunological risk and may not need desensitization
-Reference
o Leeaphorn N, Thongprayoon C, Vaitla P, Hansrivijit P, Jadlowiec CC, Mao SA, Chewcharat A, Katari S, Pattharanitima P, Boonpheng B, Kaewput W, Mao MA, Cooper M, Cheungpasitporn W. Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000-2019 UNOS/OPTN Database. J Clin Med. 2021 Jul 11;10(14):3063.
o Igbokwe M, Olatise O, Faponle A, Aremu A, Revanur V, Jiwoh H, Obajolowo O, Ameh I. Kidney Transplantation in Sickle Cell Disease Patients: Case Series and Experience from a Nigerian Kidney Transplant Center. Indian J Nephrol. 2022 Mar-Apr;32(2):164-167.
It is a great challenge to face veno-occlusive situations before or after transplantation. Homozygous patients are more likely to present clinical manifestations, increasing the risk of blood transfusions, making the patient more sensitive, and reducing the number of potential donors. Added to this are veno-occlusive conditions leading to graft injuries, functional asplenia (increased risk of infections, mainly from encapsulated bacteria), and vascular events.
Keeping target hemoglobin between 9 and 11 is recommended. Decreasing and minimizing the circulation of hemoglobin S is another important factor.
Crises with pain should be treated:
– Vigorous hydration
– Oxygen therapy (changing the shape of sickle cell hemoglobin)
– Pain control
– Assess the need for blood transfusion
It is important in the perioperative period for the patient to be well hydrated, with the disease status under control (hemoglobin electrophoresis and serum hemoglobin).
In these cases, due to the high risk of infections and aseptic bone necrosis, the ideal is to prioritize regimens without the use of corticosteroids. Induction with alemtuzumab and maintenance with mTOR plus mycophenolate may be ideal.
In cases with sickle cell trait, the risk of developing exuberant clinical conditions is very low, not interfering with the conduct of the transplant, but it is always suggestive to monitor the clinical condition and the activity of the disease.
Sickle cell disease in the transplant recipient
SCD is a hematological disease in which abnormal HbS is representing around 90% of the hemoglobin. abnormal HBS is associated with nephropathy (SCN) in around one-third to one-fourth of adult patients caused by vasoconstriction-induced medullary and cortical hypoperfusion which cause tubular damage causing tubular dysfunction in the form of proteinuria, Hematuria, Metabolic abnormalities including Hyperuricemia and hyperkalemia, nephrogenic DI, and chronic kidney disease.
Also, Acute kidney injury can occur in SCD with many causes but is commonly induced by hypovolemia, drug-induced (NSAIDS, ARBS), Vaso-occlusive crisis, or rhabdomyolysis
Eventually, CD patients end to ESRD which usually occurs at a younger age with the median age for starting RRT (being 41±14 years). ESRD can be treated by either dialysis (HD or PD) (2) or renal transplantation.
SCD on hemodialysis are exposed to higher morbidity and mortality especially as both of them cause pulmonary hypertension, on the other hand, Kidney transplantation is associated with the best outcome for SCD patients who develop ESRD (5).
· 1-year patient survival of SCD patients receiving a transplant is 88% and 10-year patient survival in SCD ESRD patients receiving kidney transplants is 56% compared to only 14% in those receiving dialysis (6).
· 1-year graft survival was reported to be around 67 – 82 %.
· high incidence of recurrence of SCD inpatients not using disease-modifying agents (8,9)
· SCD transplant recipients are exposed to higher incidences of adverse effects including (infection and steroids-induced avascular necrosis).
Preoperative
a. Anemia management and Sickling control:
target HB is around 10 gm/dl with HBS below 30%, Prophylactic anticoagulant pre and post-operative, and Using of hydroxyurea which increases HB F
b. Infection: vaccination preoperative and prophylactic antibiotics
c. Cardiological assessment and pulmonary hypertension evaluation.
Intraoperative
· Iv fluids: use a balanced solution to avoid hyper-K and metabolic acidosis and good hydration to avoid volume depletion.
Postoperative
1 Pain killers: to avoid precipitation of sickling
2 Infection: follow up sepsis parameters and early treatment
3 Monitoring of HBS level by hemoglobin electrophoresis
4 Immunosuppression management: Usually these patients develop more infection (due to asplenia) which precipitates sickling and risks patient survival also they develop avascular necrosis more commonly compared to standard recipients, so if possible better to use steroid-free protocols which can be achieved by depleting induction then maintenance dual IS using tac and MMF but again these may be difficult as most of the patients are high-risk patients with high PRA and sensitized caused by multiple blood transfusion
SCT is a benign carrier with HBS around 30% associated with a milder degree of tubular damage and a mild increase in the risk of proteinuria and CKD most of them don’t develop ESRD and if they develop ESRD they do better compared to patients without SCT with follow up
REFERENCES
1. Abbott KC, Hypolite IO, Agodoa LY. Sickle cell nephropathy at an end-stage renal
disease in the United States: patient characteristics and survival. Clin Nephrol 2002; 58:9.
2. Sharpe CC, Thein SL. How I treat renal complications in sickle cell disease. Blood 2014; 123:3720.
3. Powars DR, Elliott-Mills DD, Chan L, et al. Chronic renal failure in sickle cell disease: risk factors, clinical course, and mortality. Ann Intern Med 1991; 115:614.
4. Wong WY, Elliott-Mills D, Powars D. Renal failure in sickle cell anemia. Hematol Oncol Clin North Am 1996; 10:1321.
5. Nath J, McDaid J, Bentall A, et al. Sickle cell and renal transplant: a national survey and literature review. Exp Clin Transplant 2012; 10:1.
6. Scheinman JI. Sickle cell disease and the kidney. Nat Clin Pract Nephrol 2009; 5:78.
7. Huang E, Parke C, Mehrnia A, et al. Improved survival among sickle cell kidney transplant recipients in the recent era. Nephrol Dial Transplant 2013; 28:1039.
8. Okafor UH, Aneke E. Outcome and challenges of kidney transplant in patients with sickle cell disease. J Transplant 2013; 2013:614610.
9. Montgomery R, Zibari G, Hill GS, Ratner LE. Renal transplantation in patients with sickle cell nephropathy. Transplantation 1994; 58:618.
10. Boyle SM, Jacobs B, Sayani FA, Hoffman B. Management of the Dialysis Patient with Sickle Cell Disease. Semin Dial 2016; 29:62.
11. Han J, Zhou J, Kondragunta V, et al. Erythropoiesis-stimulating agents in sickle cell anaemia. Br J Haematol 2018; 182:602.
Again this scenario is totally new for me. Sickle cell disease is quite rare in our community especially in zone where I practice.
I have seen 5 to 7 cases of children with sickle cell disease in last 23 years of my exposure to medicine most of which had impaired physical and mental development.
‘There are no local guidelines for transplant in SCD patients and none has been transplanted yet at my center.
This was new learning experience. I went through answer of Dr. Sherif Yousef . Nice and crisp. Also went through following literature.
What is the outcome of kidney transplantation in sickle cell disease?
HbS polymerization is associated with red blood cell rigidity and vaso-occlusive events that play a fundamental role in SCD pathogenesis. chronic hemolysis with SCD and endothelial dysfunction is the key factor in the development of four major complications: acute and chronic pain, cardiopulmonary disease, central nervous system disease, and kidney disease like sick cell nephropathy (1).
SCD can present with a variety of renal involvement and its one of the leading causes of CKD with high morbidity and premature death
1. functional tubular defects with loss of urine concentration capacity and defect in urine acidification
2. Benign painless hematuria or malignant with medullary cell carcinoma
3. Proteinuria which indicates chronic sickle cell nephropathy (secondary FSGS) due to the recurrence of ischemic Vaso-occlusive crisis and chronic recurrence of renal ischemia with chronic hemolysis and endothelial dysfunction
This patient in his 50s black race with a severe and complicated course of SCD, HBSS (homozygous inheritance) including advanced CKD, and frequent blood transfusion means he had an iron overload and other end-organ damage like cardiopulmonary disease.
Both dialysis and kidney transplantation are effective renal replacement therapies for end-stage renal disease due to SCN, however, Dialysis is associated with poor prognosis with an increased risk of premature death by 7 fold compared to non-SCD ESRD patients and also less chance to go for transplantation due to limitation by cardiopulmonary fitness and sensitization due to frequent blood transfusion and exchange however Kidney transplantation is still the best option despite the inferior outcome in term of graft and patient survival if compared to non SCD recipients
So for this patient still the option of a kidney transplant is to be considered but after discussion with him the many challenges and risks including alloimmunization with the need for blood transfusion and higher risk of PNF or DGF also iron overload and sensitization with increased risk of Denovo DSA and chronic rejection, sepsis.
In one small cohort study from multiple centers in the UK, they reported that patients on an EBT program have lower HLA – sensitization risk and rejection rate with improved graft-specific outcomes and better overall patient survival in 1,5,10 years of FU compared with those, with non-EBT programs (5). also in the same series, they found in the EBT group have less risk of SCN recurrence after transplantation (5). Programmed EBT pre-transplant and after-transplantation can also contribute to a lower risk of acute vaso-occlusive crisis and of iron load
Hydroxy urea which is a cytotoxic antimetabolite that is approved for use in SCD approved for use in SCD
How do you manage his transplantation (pre, intra, and postoperative)?
Automated EBT with target HB > 9gm and reduction of HB ss< 30, regular EBT can improve the transplant outcome in such patients,
optimize hemodynamics and avoid dehydration.
Intra and post-operative hemodynamics stability with blood transfusion pre and intraoperative with antigen-matched blood transfusion
post-operative pain management, IVF management, and AB prophylaxis antiviral prophylaxis to avoid sepsis
vaccinationn to be completed prior to transplantationn
Discuss immunosuppression.
This is another challenging point in SCD recipients as they are more prone to sensitization like this patient as he had a history of frequent blood transfusion and also, he had a recurrence of sepsis
so we need to assess the degree of sensitization and may consider desensitization based on his immunological risk also with the history of recurrent sepsis we need to decide about the type of induction and triple IS (CNI, MMF, and steroid) also
Hydroxyurea is an antimetabolite and it’s an immune modulating agent that increased the HB f level its use after transplantation for patients with SCD as drug modifying agent as might reduce the vasoocculsive crisis and acute chest syndrome and also reduce the hyperfiltration and micro albuminemia so its use needs further studies ,need to be used with caution and dose adjustment as it can interact with MMF with an additive myelosuppression effect if combined with MMF or azathioprine.
Would it be different if he was heterozygous (trait)?
yes less sensitization more surgical fitness and less risk of infection or vaso-occulsive crises
References
1.Brandow AM, Liem RI. Advances in the diagnosis and treatment of sickle cell disease. J Hematol Oncol. 2022 Mar 3;15(1):20.
2. Rémy P, Audard V, Galactéros F. Rein et hémoglobinopathies [Kidney and hemoglobinopathy]. Nephrol Ther. 2016 Apr;12(2):117-29.
MOX1 and APOL1 gene variants may be associated with CKD in individuals with SCD
3.Nath KA, Hebbel RP. Sickle cell disease: renal manifestations and mechanisms. Nat Rev Nephrol. 2015 Mar;11(3):161-71.
4.Gérardin C, Moktefi A, Couchoud C, Duquesne A, Ouali N, Gataut P, Karras A, Anglicheau D, Lefaucheur C, Figueres L, Albano L, Lionet A, Novion M, Ziliotis MJ, Louis M, Del Bello A, Matignon M, Dahan K, Habibi A, Galacteros F, Bartolucci P, Grimbert P, Audard V. Survival and specific outcome of sickle cell disease patients after renal transplantation. Br J Haematol. 2019 Dec;187(5):676-680.
5. Willis JC, Awogbade M, Howard J, Breen C, Abbas A, Harber M, Shendi AM, Andrews PA, Galliford J, Thuraisingham R, Gage A, Shah S, Sharpe CC. Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion. PLoS One. 2020 Aug 13;15(8):e0236998.
Thank you, Saja
-What is the outcome of kidney transplantation in sickle cell disease?
SCD patients with ESRD can be treated with renal transplantation with variable outcomes.
Graft & patient survival:
1. Chatterjee (1980):
1-year patient survival 86%, 1-year graft survival 67%; Mortality 1st year 13%; Increased crises
2. Barber et al. (1987):
1-year graft survival 25%; Crises in 75%
3. Miner et al. (1987): Recurrent nephropathy
4. Chatterjee (1987):
1-year patient survival 88%; 1-year graft survival 82% in live, 62% in cadaveric; Increased crises
5. Montgomery et al. (1994):
1-year patient & graft survival 100%; Increased crises
6. Warady & Sullivan (1998):1-year graft survival 89% , 2-year graft survival 71%; Patient survival 89%
7. Ojo et al. (1999): DGF 24%, AR 26%, 1-year graft survival 78%, 3-year graft survival 46%, 1-year patient survival 78%, 3-year patient survival 59%
8. Bleyer et al. (2001): 1-year patient survival 90.5%, 3-year patient survival 75.0%, 1-year graft 82.5%, 3-year graft survival 53.8%
9. Abbott et al. (2002): Risk of mortality same as in transplanted non SCD
10.O’Rourke et al. (2008): Recurrent allograft dysfunction from vascular congestion & tubular necrosis
11.Scheinman (2009): 10-year patient survival 56%
12.Kim et al. (2011): Intragraft sickle cell vaso-occlusive crisis as a cause of early allograft loss
//////////////////////////////////////
·How do you manage his transplantation (pre, intra and postoperative)?
Perioperative management:
The operating & anesthesia teams should be aware of the diagnosis of a SCD & the need for special attention in these patients.
Ensure a preoperative Hb of 10 g/dL.
Reduce hyperviscosity; there may be a need for exchanging blood transfusion.
Minimize alloimmunization by giving antigen-matched blood.
Monitoring of intake & output, hematocrit, peripheral perfusion, & oxygenation status.
Intraoperative monitoring of BP, cardiac rhythm & rate, & oxygenation.
A minimum of 8 hours of preoperative hydration, with intraoperative monitoring of temperature, BP, ECG, & oxygenation; these measures can reduce the frequency of sickling & vasoocclusive crises.
Postoperative care:
Attention to hydration
O2 administration with careful monitoring, & respiratory therapy.
Strict monitoring of patients wellbeing, renal function, drug level, etc.
//////////////////////////////////////
Discuss immunosuppression?
A. The auto- or iatrogenic (following hypersplenism &/or sequestration crises) splenectomy is associated with significant immunodeficiency; thus challenging the choices of immunosuppression therapy in SCD patients following KTX.
B. Optimal control of infection requires:
1. Adequate prophylactic measures including use of pre- & post-exposure vaccination, & antibiotics.
2. Barrier nursing, intensive post op management, strict personal & environmental hygiene
3. Drug monitoring
4. Surveillance & screening for infections & malignancies
5. Early therapeutic interventions
6. Infection control.
C. Multiple blood transfusions (because of the prevalent anemia & crises) make SCD patients more susceptible to develop various immuno-reactions including graft rejection, thus making donor /organ selection more challenging; however, rejection (hyperacute, acute, & chronic) was not significantly different from non-SCD patients. This is due to different measures including:
-Limiting transfusion unless very necessary
-Strict screening for antibodies
-Typing & strict matching of donor & recipient
-Plasmapheresis
-Leukodepletion
-Induction immunosuppression
– Appropriate immunosuppressive therapy
//////////////////////////////////////
·Would it be different if he was heterozygous (trait)?
Generally, persons with SCT do not have any of the symptoms of SCD & live a normal life; so management of transplantation in this category of patient shouldn’t differ much from that of the general population.
References
U. H. Okafor and E. Aneke Review Article: Outcome and Challenges of Kidney Transplant in Patients with
Sickle Cell Disease. Journal of Transplantation Volume 2013, Article ID 614610, 8 pages http:// dx.doi.org/10.1155/2013/614610
Thank you, Mohamed
survival of SCD patients following KT has improved with no significant
overall survival difference between SCD patients and controls (ESRD patients from other
Patient survival has improved among contemporary sickle cell recipients compared with
an earlier cohort and is comparable to a matched cohort of diabetic kidney recipients.(2).
preop:
cell syndrome and the need for special attention in the patient.
for a period of 3 months and repeat the cross-matches in order to rule out the presence of new antibodies or plasma exchange.
influenza virus are strongly recommended at least 2 weeks before transplant surgery.(1)
Intraoperative:
peri-allograft collection.
Postoperative :
Depend on level of DSA either ATG or Basiliximab will be use .
In sensitized patient PF and IVIG.
Maintenance Prednisolone ,TAC and MMF.
Nephropathy had been reported to be far less frequent and severe in HbSC and HbAS
than other phenotypes .They require less transfusion so less risk of sensitization.
otherwise operative precaution is similar to SCSS.
References:
1- Christel Gerardin et al Survival and specific outcome of sickle cell disease patients
after renal transplantation. Br J Haematol. 2019 Dec;187(5):676-680.
2- Edmund Huang et al .Improved survival among sickle cell kidney transplant recipients
in the recent era. Nephrol Dial Transplant2013 Apr;28(4):1039-46.
Thank you, Mohamed
What is the outcome of kidney transplantation in sickle cell disease?
How do you manage his transplantation (pre, intra and postoperative)?
Pre-transplantation:
Intraoperative:
Post transplantation
Discuss immunosuppression?
The management protocol for a recipient with sickle cell trait would be similar to a recipient with ESRD due to any cause
References
Leeaphorn, N.;Thongprayoon, C.; Vaitla, P.; Hansrivijit, P.; Jadlowiec, C.C.; Mao, S.A.; Chewcharat, A.; Katari, S.; Pattharanitima, P.; Boonpheng, B.;et al. Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000–2019 UNOS/OPTN Database. J. Clin. Med. 2021, 10, 3063. https://doi.org/10.3390/jcm10143063
Martin Igbokwe, Olalekan Olatise, 1 Adegboyega Faponle, 1 Abayomi Aremu, Vasanth Revanur, Habiba Jiwoh, 1 Omotola Obajolowo, 1 and Idaomeh Ameh 1
Indian J Nephrol. 2022 Mar-Apr; 32(2): 164–167. Published online 2022 Mar 9. doi: 10.4103/ijn.IJN_28_20
Thankyou well done are you going to totally replace MMF with hydroxy urea or reduce MMF dose and follow WBC count?
*Regarding out-come post-kidney transplantation: Patients will be highly sensitized due to repeated blood transfusion so high incidence of acute rejection episodes, bad graft survival But , Patient survival is still better than patients with CKDVd on dialysis.
*Managing this transplantation case: In SCD , Vaso-occlusive crisis could occur with sub-sequent complications: papillary necrosis, hematuria , FSGS , anemia and Diabetes insibidus.
I.Pre-operative management: 1.Target hemoglobin must be around 10gm/dl, but reduce blood transfusion to decrease incidence of sensitization by giving Epo agents. Allo-sensitization can be minimized by giving antigen-matched blood.
2.Vaccinations ( Pneumococcal, Miningococcal ACWY , Meningococcal serogroup B , Hemophilus infl. type B , Influenza) should be taken 2 weeks to month before surgery because of auto-splenectomy from repeated attacks of vaso-occlusive crisis.
II-During surgery and post-transplant:
During operation : gentle dissection, meticulous hemostasis, and short warm and cold ischemia times as possible , good hydration , give morphine-controlled analgesia to avoid pain-induced crisis, antibiotic therapies , thromboprophylaxis, blood transfusion may be needed.
& Post transplant hydroxyurea may decrease SCD related allograft injury by pssible reducing proteinuria ,but combination with MMF should be cautiously taken.
Co-trimoxazole for six months, valganciclovir and antifungal could also be used as a prophylaxis.
BMT recently considered novel therapy for SCD.
Genetic therapy could be used recently with promising results : CRISPR gene correction therapy.
*Regarding immunosuppression : The same protocol of immunosuppression will be used , because of highly sensitization so; need desensitization induction with ATG is a must followed by maintenance therapy with steroids, CNI and MMF.
*If it was hetero-zygous( trait), management will not differ: sickle cell trait may cause also papillary necrosis or hematuria also as SC disease but less severer , low immunological risk so may be no need for desensitization protocol.
*References:
1. Ojo AO, Govaerts TC, Schmouder RL,etal.: Renal transplantation in end-stage sickle cell nephropathy. Transplantation. 1999 Jan 27;67(2):291-5.
2.Gérardin C, Moktefi A, Couchoud C, et al.: Survival and specific outcome of sickle cell disease patients after renal transplantation. Br J Haematol. 2019;187:676–80.
3.Huang E, Parke C, Danovitch G, et al.: Improved survival among sickle cell kidney transplant recipients in the recent era. Nephrol Dial Transplant. 2013;28:1039–46.
4.Okafor UH, Aneke E. Outcome and challenges of kidney transplant in patients with sickle cell disease. J Transplant.2013:614610.
Thankyou what is the situation with MMF and hydroxy urea ,can it replace MMF?
What is the outcome of kidney transplantation in sickle cell disease?
There are concerns about inferior outcomes for kidney transplant recipients with SCD compared to non-SCD recipients, despite improvements in survival following transplantation in SCD patients.
1-reduced allograft compared to non-SCD kidney transplant recipients
2-patient survival compared to non-SCD kidney transplant recipients
As SCD is characterized by :
vaso-occlusion, especially in the kidneys , resulting in kidney infarction
papillary necrosis
Hematuria
focal segmental glomerulosclerosis
diabetes insipidus
Anemia may further speed up the decrease of kidney function by reducing oxygen delivery.
How do you manage his transplantation (pre, intra and postoperative)?
Pre-Operative :
1- Vaccinations : ( for hyposplenism from autosplenetomy )
At least 2 weeks before surgery against (S. pneumonia – N. meningitides -H. influenza type b- influenza virus )
2- Anemia :
To reduce the need for blood transfusions, erythropoietin stimulation can be started months before surgery to gradually treat anemia with target Hb level 9 :11 gm/dl
3- Desensitization prior to transplant :
many sickle patients are at high immunological risk, necessitating desensitisation prior to transplant
4- all potential donors :
Anyone with a mutant sickle cell gene is excluded with AA donors favored
Intra Operative and early post operative :
During operation : (gentle dissection, thorough hemostasis, and short warm and cold ischemia times )
optimal hydration
Adequate analgesia (morphine-based patient-controlled analgesia was ensured to avoid pain-induced crisis )
Antibiotic therapies
Thromboprophylaxis
Blood transfusion or blood exchange:
may be needed in severe anemia or aplastic crisis or Veno occlusive crisis .
Hydroxyurea :
Although there is little evidence on how hydroxyurea affects kidney transplant allografts, it has showed promise in reducing proteinuria, stabilising kidney function, and lowering mortality risk in SCD patients who do not had kidney transplants.
Other Therapies :
Bone marrow transplantation has recently emerged as a novel treatment for SCD
Genetic approaches against SCD such as CRISPR gene correction therapy are promising, investigation in this area is still in the early stages
Discuss immunosuppression?
Most of patients ith SCD are sensitized or at risk of blood transfusion after operation so ATG induction with ( steroids + MMF + Tacrolimus ) as maintenance therapy
Would it be different if he was heterozygous (trait)?
Less risk of anemia than homozygous types >> less amenable for blood transfusion >> so less risk for sensitization.
Less risk of veno-occulsive crisis – anemia – hypoxia .
References
Gérardin C, Moktefi A, Couchoud C, Duquesne A, Ouali N, Gataut P, et al. Survival and specific outcome of sickle cell disease patients after renal transplantation. Br J Haematol. 2019;187:676–80.
Bonanni P, Grazzini M, Niccolai G, Paolini D, Varone O, Bartoloni A. Recommended vaccinations for asplenic and hyposplenic adult patients. HumVaccines Immunother. 2017;13:359–68.
Huang E, Parke C, Mehrnia A, Kamgar M, Pham PT, Danovitch G, et al. Improved survival among sickle cell kidney transplant recipients in the recent era. Nephrol Dial Transplant. 2013;28:1039–46.
Thankyou for the genetic approach studies.
Sickle cell disease (SCD) has been shown to be associated with decreased patient survival and death censored graft survival (hazard ratio of 2.87 and 1.98 respectively) in comparison with ESRD due to diabetes mellitus, hypertension or glomerular disease (1).
Review article by Okafor et al have shown that the short-term and long-term outcomes in patients with SCD are comparable to those with HbAA (2). Another review showed that the 1-year graft survival as similar in patients with SCD and those without SCD, although the patient survival was lower (3).
Use of exchange blood transfusions (EBT) in SCD patients improved patient and graft survival as well as graft function, without increasing the risk of DSA formation (4).
The index patient is an Afro-Caribbean is CKD4 with history of multiple blood transfusions. Transplant surgery in such a patient involves multidisciplinary approach with involvement of hematologist, nephrologist, transplant surgeon and the anesthetist.
Donor selection is important as usually in a living donor program family members come forward for donation. The donor should be evaluated for presence of sickle gene.
The pre-operative management will include:
a) Routine pre-transplant work-up as advised for a kidney transplant recipient should be done.
b) Blood grouping, HLA typing and cross-match, including single antigen bead testing for DSA (in view of sensitization events – multiple blood transfusions). Avoid ABO incompatible transplants. Allo-sensitization can be minimized by giving antigen-matched blood till sickle-cell preparation is negative (4).
c) Transplant recipient should be vaccinated against S. pneumoniae, N. meningitidis, H. influenza type B, and influenza virus, at least 2 weeks prior to surgery (5,6).
d) A target pre-operative Hb of 10-11 g/dl.
e) Keeping HbS less than 20% (to reduce hyperviscosity and resultant Vaso-occlusive crisis): It can be achieved by giving exchange blood transfusion, usually started 2 weeks prior to transplant (7,8).
f) Desensitization with plasmapheresis and IVIG in the event of DSA presence.
g) Pre-operative monitoring of intake-output, hematocrit, oxygenation status and peripheral perfusion.
Intra-operative management:
a) The operative and anesthetic team must be aware of the sickle cell disease status of the patient.
b) Intra-operative monitoring of blood pressure, oxygenation with 40% O2, heart rate and rhythm is crucial.
c) Warming the graft with saline at 37 degree Celsius before completing the arterial anastomosis, discarding 200 ml of the recipient blood through gonadal vein before ligating it (4,8).
d) Dopamine infusion at 4 microgram/kg/min during and immediately after transplant.
e) Extra intravenous fluid to reduce blood viscosity, supplemental oxygen, and use of erythropoietin until auto-production is sufficient (4).
f) In presence of sickle cell crises, intravenous fluids and partial exchange transfusions will be required (4).
g) Anti-thymocyte globulin as induction agent and use of hydroxyurea as immunosuppressant (in place of azathioprine) which will help in stimulating fetal hemoglobin (7,9).
Post-operative management:
a) Intensive monitoring with respect to hydration, oxygenation, as well as respiratory therapy (4).
b) Important to maintain strict asepsis in view of increased risks of sepsis induced sickle cell crises.
c) Close follow-up post-discharge.
d) Antibiotic, antifungal and antiviral prophylaxis as per the standard protocols should be given.
Prior multiple blood transfusions invariably leads to allo-sensitization, leading to requirement of desensitization in presence of DSAs. ATG induction and triple drug immunosuppression (Tacrolimus, MMF and steroids) is required. Hydroxyurea can be used in place of MMF due to added advantage of increasing fetal hemoglobin. In view of risk of avascular necrosis, early steroid withdrawal can be considered (5,7,8).
Sickle cell trait patient would not have required multiple blood transfusions, decreasing the risks of allo-sensitization. The management protocol for a recipient with sickle cell trait would be similar to a recipient with ESRD due to any cause. Studies have shown poorer graft and patient outcomes in patient with sickle cell trait, as compared to SCD (8).
References:
1) Leeaphorn N, Thongprayoon C, Vaitla P, Hansrivijit P, Jadlowiec CC, Mao SA, Chewcharat A, Katari S, Pattharanitima P, Boonpheng B, Kaewput W, Mao MA, Cooper M, Cheungpasitporn W. Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000-2019 UNOS/OPTN Database. J Clin Med. 2021 Jul 11;10(14):3063. doi: 10.3390/jcm10143063. PMID: 34300230; PMCID: PMC8305507.
2) Okafor UH, Aneke E. Outcome and challenges of kidney transplant in patients with sickle cell disease. J Transplant. 2013;2013:614610. doi: 10.1155/2013/614610. Epub 2013 Apr 11. PMID: 23691273; PMCID: PMC3649443.
3) Ojo AO, Govaerts TC, Schmouder RL, Leichtman AB, Leavey SF, Wolfe RA, Held PJ, Port FK, Agodoa LY. Renal transplantation in end-stage sickle cell nephropathy. Transplantation. 1999 Jan 27;67(2):291-5. doi: 10.1097/00007890-199901270-00018. PMID: 10075596.
4) Willis JC, Awogbade M, Howard J, Breen C, Abbas A, Harber M, Shendi AM, Andrews PA, Galliford J, Thuraisingham R, Gage A, Shah S, Sharpe CC. Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion. PLoS One. 2020 Aug 13;15(8):e0236998. doi: 10.1371/journal.pone.0236998. PMID: 32790687; PMCID: PMC7425908.
5) Igbokwe M, Olatise O, Faponle A, Aremu A, Revanur V, Jiwoh H, Obajolowo O, Ameh I. Kidney Transplantation in Sickle Cell Disease Patients: Case Series and Experience from a Nigerian Kidney Transplant Center. Indian J Nephrol. 2022 Mar-Apr;32(2):164-167. doi: 10.4103/ijn.IJN_28_20. Epub 2022 Mar 9. PMID: 35603115; PMCID: PMC9121718.
6) Bonanni P, Grazzini M, Niccolai G, Paolini D, Varone O, Bartoloni A, Bartalesi F, Santini MG, Baretti S, Bonito C, Zini P, Mechi MT, Niccolini F, Magistri L, Pulci MB, Boccalini S, Bechini A. Recommended vaccinations for asplenic and hyposplenic adult patients. Hum Vaccin Immunother. 2017 Feb;13(2):359-368. doi: 10.1080/21645515.2017.1264797. PMID: 27929751; PMCID: PMC5328222.
7) Brennan DC, Lippmann BJ, Shenoy S, Lowell JA, Howard TK, Flye MW. Living unrelated renal transplantation for sickle cell nephropathy. Transplantation. 1995 Mar 15;59(5):794-5. doi: 10.1097/00007890-199503150-00029. PMID: 7886811.
8) Nath J, McDaid J, Bentall A, Ball S, Ready AR, Inston NG. Sickle cell and renal transplant: a national survey and literature review. Exp Clin Transplant. 2012 Feb;10(1):1-7. doi: 10.6002/ect.2011.0098. PMID: 22309412.
9) Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22. doi: 10.1056/NEJM199505183322001. PMID: 7715639.
Thankyou well done
Checked the reference and true they stated that outcome in Tx is worse in SC trait than SCD !!
What is the outcome of kidney transplantation in sickle cell disease?
· Sickle cell disease often leads to ESKD, could be due to chronic intestinal fibrosis, but FSGS and nephrotic syndrome may occur
· Short-term patient and graft survival rates are not different from those in patients without sickle cell disease
· long-term outcomes of patients with sickle cell disease have been shown to be comparable to matched control patients with diabetes
· Sometimes severe, sickling crises may occur after transplantation, could be due to the improving hematocrit.
· Survival for transplanted patients with sickle cell disease may improve, compared with sickle cell disease patients who remain on the waiting list
How do you manage his transplantation (pre, intra and postoperative)?
Pre-operative care:
1. PREVENTION AND TREATMENT OF VASO-OCCLUSIVE EVENTS AND THEIR COMPLICATIONS
· hydroxyurea is a mainstay in the overall management of individuals with SCD, since it reduces the incidence of acute vaso-occlusive pain episodes and other vaso-occlusive events including acute chest syndrome and in some cases stroke; decreases hospitalization rates; and prolongs survival
2. INFECTION PREVENTION
· Immunizations: a cornerstone of infection prevention in SCD.
-People with SCD have increased morbidity and mortality from COVID-19, and COVID-19 vaccination is recommended.
-Annual seasonal influenza vaccination should also be provided.
3. Patients with sickle cell disease presenting for elective surgery should be reviewed in a pre-assessment clinic, with input from the nominated lead haematologist
4. The acute pain team should be notified in advance if a patient with sickle cell disease is undergoing major surgery, particularly if the patient has a history of chronic pain.
5. Patients with sickle cell disease should be scheduled early on the operating list to avoid prolonged starvation
6. Preoperative transfusions until the HbS percentage is less than 20 (or exchange transfusion where necessary), ( 2 weeks before the transplant date, for living transplant)
7. Recipient preoxygenation with 40% O2, continued for 48 hours after the operation.
Peri and post operative management
· Ensure the operating and anesthesia teams are aware of the diagnosis of a sickle cell syndrome and the need for special attention in the patient.
· Ensure that patients preoperative haemoglobin of 10 g/dL is achieved.
· Reduce hyperviscosity especially in patients with SCD-SC; there may be a need for exchanging blood transfusion.
· Minimize alloimmunization by giving antigen-matched blood.
· Preoperative monitoring of intake and output, hematocrit, peripheral perfusion, and oxygenation status.
· Intraoperative monitoring of blood pressure, cardiac rhythm and rate, and oxygenation.
· Intensive postoperative care including attention to hydration, oxygen administration with careful monitoring, and respiratory therapy.
· Thorough follow up of patients with strict monitoring of patients wellbeing, renal function, drug level, and so forth.
Discuss immunosuppression?
tacrolimus, mycophenolate mofetil, and prednisolone with basiliximab on induction and day 4 in ABO compatible allografts. Suggested by :
http://www.ectrx.org/forms/ectrxcontentshow.php?year=2012&volume=10&issue=1&supplement=0&makale_no=0&spage_number=1&content_type=FULL%20TEXT#:~:text=Sickle%20Cell%20and,Nicholas%20G.%20Inston
· mTOR inhibitors associated with hydroxyurea given to a patient who had undergone kidney transplantation and had SCD seemed to improve clinical and biological outcomes
https://onlinelibrary.wiley.com/doi/10.1111/ajt.14263#:~:text=Improved%20Fetal%20Hemoglobin,A.%20Del%20Bello
Would it be different if he was heterozygous (trait)?
· Sickle cell trait likely has an increased risk of chronic kidney disease (CKD), a more rapid decline in estimated glomerular filtration rate (EGFR), and an increased incidence of albuminuria. Two large studies from 2022 analyzed the impact of sickle cell trait on CKD
· Sickle cell trait is likely a risk factor for hyposthenuria, which can lead to dehydration, as well as chronic kidney disease (CKD) and end-stage kidney disease (ESKD), as well as proteinuria, hematuria, renal medullary carcinoma (extremely rare)
· Data are conflicting regarding increased risks of hypertension and diabetes. Coronary heart disease, myocardial infarction, and heart failure are no different from controls
· concerns have been raised regarding increased risks of rhabdomyolysis and possibly increased mortality in the setting of intensive physical training in individuals with sickle cell trait compared with the general population
SIXTH EDITION Handbook of Kidney Transplantation Edited by Gabriel M. Danovitch, MD
https://europepmc.org/article/pmc/8305507#sec5-jcm-10-03063:~:text=Outcomes%20of%20Kidney,Cheungpasitporn%20W2
https://pubmed.ncbi.nlm.nih.gov/35461807/#:~:text=Sickle%20Cell%20Trait,5
Thankyou ,good review of SC trait.
do you know their incidence in AA,Africa ,Arab peninsula?
Are they prone to complications under stressful conditions?
1_ as regard the outcomes of kidney transplantation in sickle cell disease, it is inferior to other causes of ESKD however, it is better than staying on HD on the waiting list.
2_ pretransplantation management:
_proper counseling of the patient.
_ proper selection of the donor (screening and diagnosis of heterozygous state if any living related donor).
_ avoid any additional risk of sensitization as ABO or HLA incompatible transplantation.
_ vaccination against capsulated organisms (pneumococci, meningococci and hemophilus influenza type B) at least 6 weeks before transplantation.
_ those patients have autosplenectomy (so susceptible to many infections especially after start of immunosupressive therapy), annual influenza vaccine after tranplantation is essential
_ target HB level is 9_11 gm/dl, with target HB S less than 30 %, so partial exchange transfusion is needed to achieve the target.
—Intraoperative management.
– ensure adequate hydration, oxygenation and temperature.
_Postoperative care:
_ follow up of hydration state and good fluid resuscitation.
_ adequate analgesia.
_ check HB
_prophylactic antiplatlet therapy
_ use of hydroxyurea to to decrease HB S
_ prophylactic septazole against pneumocystis jiroveci and valganciclovir against CMV are crucial.
3_ Management of immunosupressive therapy:
– use of induction therpy with ATG , due to expected risk of alloimmunization by frequent transfusion therapy.
-use of tac based triple maintenance immunosupressive therapy (with early steroid withdrawal).
4_ If he is heterozygous , the risk of allosensitization will be absent as he will be transfusion independent.
So better graft and patient survival.
.
I enjoyed reading your informative write-up. Scientifically it is very good.
Ajay
Patients with SCD may have limited access to transplantation due to repeated blood transfusion and allosensitization, they are more predisposed to infection and will be at increased risk with immunosuppression
Kidney transplantation is associated with better prognosis than dialysis in patients with SCD and ESRD but the overall patient and graft survival post transplant is inferior when compared to other counterparts in the ESRD population as a whole.
A retrospective study showed that patient and graft survival were better in patients treated with automated exchange blood transfusion (EBT) post transplant with lower rate of SCN recurrence, no increase HLA sensitization or rejection despite increased blood transfusion.
EBT program pre and post transplant may improve patient and graft outcome but is not widely available in all centers.
Preoperatively, we should ensure keeping Hgb of 10g/dL, reduce hyperviscosity giving antigen matched blood to decrease alloimmunization.
Intraoperatively, the operating and anesthesia team should be aware of CSD, monitoring of intake and output, hematocrit, peripheral perfusion and oxygenation .
Intensive post operative care with careful hydration, oxygenation and respiratory therapy.
Treatment with regular EBT aiming to keep HbS level <30%
They usually receive the same regimen of immunosuppression, induction with anti thymoglobulin is preferred due to increased risk of allosensitization.
Maintenance with prograf, mycophenolate and steroids with rapid tapering of steroids
Post transplant hydroxyurea may decrease SCD related allograft injury but should be used cautiously with mycophenolate
The management will be the same, data on outcome of SCT who have kidney transplantation is limited
SCT is associated with multiple kidney complications, less severe than SCD, include impaired urinary concentration, hematuria and papillary necrosis.
Gerardin C, Moktefi A, Couchoud C, Duquesne A, Ouali N, Gataut P, et al. Survival and specific outcome of sickle cell disease patients after renal transplantation. Br J Haematol. 2019; 187: 676–680.
Huang E, Parke C, Mehrnia A, Kamgar M, Pham P-T, Danovitch G, et al. Improved survival among
sickle cell kidney transplant recipients in the recent era. Nephrol Dial Transplant. 2013; 28: 1039–1046.
Willis JC, Awogbade M, Howard J, Breen C, Abbas A, Harber M, Shendi AM, Andrews PA, Galliford J, Thuraisingham R, Gage A. Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion. Plos one. 2020 Aug 13;15(8):e0236998.
Okafor UH, Aneke E. Outcome and challenges of kidney transplant in patients with sickle cell disease. Journal of transplantation. 2013 Jan 1;2013.
Sharpe, Claire C. MBBS, PhD1,2; Suddle, Abid MBBS, MD3; Stuart-Smith, Sara MBBS, MD4. An Overview of Solid Organ Transplantation in Patients With Sickle Cell Disease. Transplantation: October 10, 2022 – Volume – Issue – 10.1097
Ataga KI, Saraf SL, Derebail VK. The nephropathy of sickle cell trait and sickle cell disease. Nature Reviews Nephrology. 2022 Jun;18(6):361-77.
I enjoyed reading your comprehensive write-up.
Ajay
What is the outcome of kidney transplantation in sickle cell disease?
How do you manage his transplantation (pre, intra and postoperative)?
Discuss immunosuppression?
Would it be different if he was heterozygous (trait)?
I enjoyed reading your informative write-up. Scientifically it is very good.
Ajay
thank you sir
Sickle disease (SCD) is an inherited disease that affects the kidneys in a progressive manner leading to microalbuminuria and unable to concentrate the urine. As the kidney disease worsens the proteinuria worsens to overt proteinuria and causes a decline in kidney function. About 50% of SCD patients develop CKD and the prevalence of ESRD ranges from 5-18% with a median age of 23 years. It is noted that even though there is a high number of ESRD with SCD there are not many transplant patients. Different studies have shown different results as it concerns SCD and transplantation. Based on a study utilizing the UNOS/OPTN database from 2000-2019 that patients with kidney transplant recipients with SCD had lower death-censored graft survival and increase mortality when compared with non-SCD recipients. However, there was no significant difference in the allograft and patient survival between the recent era in 2010-2019 versus the early time around 2000-2009.
The reasons why there is an increase in allograft loss in SCD are:
1) Vaso-occlusion
2) Papillary necrosis
3) Haematuria
4) FSGS
5) Diabetes insipidus
If the kidneys transplantation is successful the allograft will still be affected by the SCD through various mechanisms:
1) Iron/heme deposits in the proximal tubules.
2) Chronic allograft injury and anemia may worsen the kidney functions
3) Hypoxia
4) Allograft thrombosis.
With all the mentioned above, there is a persistent lower allograft survival among kidney transplant recipients with SCD compared with those with non-SCD.
Medications like hydroxyurea have reduced proteinuria and stabilized kidney functions and reduce mortality. However, as it relates to blood transfusion, it has not benefited the recipient but increases immunological risk and increases the risk of rejection. So allograft survival in SCD kidney recipients was worse than other regular recipients.
PRE:
ü SCD patients who are willing to get kidney transplantation will need a multidisciplinary team to be able to manage and prepare.
ü Pre-transplantation blood transfusion must be avoided as much as possible to prevent alloimmunization.
ü Use ESA to stimulate blood increase. All patients with sickle cell disease have a steady state and the Hb range should be about 9-10g/L
ü Ensure the use of hydroxyurea
ü Ensure PRA is negative and that the reduced HLA mismatch
ü Up-date vaccinations
ü Ensure proper hydration
ü Physiotherapy
INTRAOPERATIVE:
ü Antibiotic prophylaxis may be needed
ü Avoid too many fluids
ü Monitor vitals
ü Avoid too much blood lost
ü Shorten the warm and cold ischemic time
POST operative:
ü Ensure the patient is kept warm
ü Avoid fluid overload
ü Pain control management
ü Continue antibiotic therapies
ü Monitor vitals
ü Monitor hemoglobin levels
ü Thrombosis prophylaxis
Consider the use of ATG as the plan of induction with a combination of CNI, MMF, and steroids. Steroids must be monitored closely and dose reduction must be considered early.
Sickle trait outcome is similar to other patients. So I think the management would be similar to other recipients, not SCD.
Leaphorn, N., et al. Journal of clinical medicine (2021). Outcomes of kidney transplant recipients with sickle cell disease: an analysis of the 2000-2019 UNOS/OPTN database. 2021 Jul; 10(14): 3063.
Thankyou well done but remember it is nephrogeic DI
The increased risk of allograft loss in SCD kidney transplant recipients is likely multifactorial.
-SCD is characterized by vasooclusion, especially in the kidneys, resulting in kidney infarction,
-papillary necrosis,
-hematuria,
-focal segmental glomerulosclerosis,
-diabetes insipidus.
Successful kidney transplantation significantly improves kidney function among ESKD patients with SCD.
the kidney allograft can still be affected by SCD
evidenced by iron/heme deposition in proximal renal tubules and related acute tubular injury in the kidney allograft biopsies
In addition, chronic allograft injury and anemia may accelerate kidney function decline by limiting oxygen delivery.
Hypoxia may also lead to the formation of a reactive oxygen species that potentiates tissue inflammation
Furthermore, allograft thrombosis during sickle cell crisis after kidney transplantation has been reported
Among kidney transplant recipients with SCD, study ensured the safety of long-term automated exchange blood transfusions (EBT) with improvement in allograft and patient outcomes and no increase in antibody formation or allograft rejection
Once a patient is listed for renal transplantation, s/he should be started on
regular blood transfusion (preferably EBT), which improves their well-being and fitness for surgery while awaiting transplantation.
Patients on regular EBT posttransplantation have better graft survival and fewer adverse events, including painful crises and acute sickle nephropathy.
-Following 2 weeks of delayed graft function, recovery of GFR was accompanied by a rapid rise in hemoglobin leading to frequent VOC, a complication that the patient had not suffered from for more than 10 years and one that is well recognized after renal transplantation.
47
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Thankyou Esraa so what are your precautions to avoid VOC meaning what HB levels that you should not exceed by EBT?
Thank you dr dawlat , target hb not more than 11 g/dl
What is the outcome of kidney transplantation in sickle cell disease?
–Outcome of kidney transplant in these SCD patients is variable.
-SCD ESKD patients receive a survival benefit following KT compared to dialysis, one-year patient and graft survival of 87% and 67%, respectively
-Earlier reports on KT in SCD patients suggested poor allograft survival and non-SCD KT- recipient.
-There was a trend toward improved survival in SCD- KTR
-Later studies have reported graft and patient survival rates comparable to those of nondiabetic patients with normal haemoglobin genotype.
Analysis of the 2000–2019 UNOS/OPTN Database showed:
-Patient and allograft survival in SCD kidney recipients were worse than non-SCD recipients.
-SCD was associated with :
significantly lower patient survival HR 2.87
Death-censored graft survival HR 1.98 compared to non-SCD recipients.
– In adjusted analysis, SCD recipients were significantly associated with:
lower 1-year death-censored graft survival HR 2.22.
lower 1-year patient survival than non- SCD recipients with HR of 2.24 although it did not reach statistical significance
– There was no significant difference in death censored graft survival HR 0.99 and patient survival HR 0.93of SCD recipients in the recent versus early era.
One study in London Joanna et al. showed overall 1, 5- and 10-year patient survival was 91%, 72% and 33% respectively, with death- censored graft survival at 87%, 61% and 19%.
All these finding should not discourage kidney transplantation for ESKD patients with SCD due to a known survival benefit of transplantation compared with remaining on dialysis.
How do you manage his transplantation (pre, intra and postoperative)?
Patient with SCD need MDT approach due to their multiple orang involvement, ensure the teams are aware of the diagnosis of a SCD and the need for special attention in the patient (nephrologist, surgeon, hematologist, cardiologist, pulmonologist and anesthetist.
Pre-operative considerations:
– Ensure preoperative Hg of 10 g/dL.
– Reduce hyper-viscosity by keeping HgS < 20 % , may need exchange transfusion, at least 2 weeks before the transplant date
-Minimize alloimmunization by giving antigen- matched blood
-If require blood transfusion; to delay for a period of 3 months and repeat the cross-matches.
-Repeated transfusion contributed to the positive DSA titers, which necessitated plasma exchange and immunoglobulin administration for desensitization.
– Donor selection is also a very important key factor, genotypes of all potential donors are requested and anyone with the abnormal sickle cell gene is excluded with AA donors favored
– Cardiovascular risk evaluation: ECG, echocardiogram.
– Pulmonologist evaluation with consideration for; PFT, CT chest.
– Vaccinations against S. pneumoniae, N. meningitidis, H. influenza type b, and influenza virus are strongly recommended at least 2 weeks before transplant surgery.
– Thromboprophylaxis are all important for achieving good results.
-Use of hydroxyurea (increases HbF while reducing the HbS).
– Preoperative adequate hydration and oxygenation status.
Intraoperative considerations:
– Careful selection of anesthetic agent, as it may worsen the hypoxic state and can precipitate VOC
– Intraoperative monitoring of temperature, blood pressure, cardiac rhythm and rate.
– Adequate intraoperative oxygenation.
– Strict monitoring of fluid balance
– Optimal hydration.
– Adequate analgesia.
– Surgically, gentle dissection, meticulous hemostasis.
– Short warm and cold ischemic time.
– Infusion of dopamine at 4 ìg/kg/min during and after transplant, is advocated.
-During back bench preparation the kidney is cold perfused in the normal fashion, and a surgical clip placed over the gonadal vein and is not ligated.
-Before completion of the arterial anastomosis, 37°C saline is infused through the renal artery and vented through the gonadal vein.
-Once the vented solution feels sufficiently warmed, the arterial anastomosis completed, and 200 mL of recipient blood is vented in the same fashion and discarded followed by ligation of the gonadal vein.
Postoperative considerations:
-Intensive postoperative care including attention to: hydration, oxygenation and respiratory condition.
– Liberal morphine-based patient-controlled analgesia was ensured to avoid pain-induced crisis.
– Septicemic complications are a common cause of perioperative mortality in SCD.Therefore, measures in control of infection include barrier nursing, intensive post op management, strict personal and environmental hygiene, surveillance and screening for culprit infections, the need for use of wound drains inserted intraoperatively and aggressive drainage of the peri-allograft collections
– Careful monitoring of patients wellbeing, renal function, drug level.
– Thromboprophylaxis.
For patients who develop sickle crises, IV fluid and partial exchange transfusions, also have been suggested.
· Discuss immunosuppression?
Due to repeated blood transfusion and high level of sensitization, the use of ATG on induction is advisable.
The use of hydroxyurea in preference of azathioprine with the dual purpose of immunosuppression and stimulation of fetal hemoglobin.
Some recommended the usual IS based on current unit guidelines of tacrolimus, mycophenolate mofetil, and prednisolone with basiliximab on induction and day 4 in ABO compatible allografts.
Considerations for early steroid withdrawal, risk of AVN.
· Would it be different if he was heterozygous (trait)?
SCT is associated with renal dysfunction, less severe than in SCD.
Hematuria and impaired urinary concentration are the most-common signs of renal involvement.
Increased urinary tract infections may be associated.
Renal medullary carcinoma is a tumor seen almost exclusively in sickle cell trait patients.
More prone for VET and careful monitoring and proper anticoagulation.
References:
-Okafor, U. H., and E. Aneke. “Outcome and challenges of kidney transplant in patients with sickle cell disease.” Journal of Transplantation 2013 (2013).
-Leeaphorn N, Thongprayoon C, Vaitla P, et al. Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000-2019 UNOS/OPTN Database. J Clin Med. 2021;10(14):3063. Published 2021 Jul 11. doi:10.3390/jcm10143063.
– Joanna C. Willis, Moji Awogbade, JO Howard, et al. Outcome following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion. PLoS ONE. 2020; 15(8)
– Martin Igbokwe, Olalekan Olatise, Adegboyega Faponle et al. Kidney transplantation in sickle cell disease patient: Case series and experience in from a Nigeria kidney transplant centre. Indian J. Nephrol. 2022; 32: 164-7
– Jay Nath et al /Experimental and Clinical Transplantation (2012) 1: 1-7
Thankyou Hadeel this is a model answer covering all aspects completely specially the intra operative maintenance of the graft temperature,also the potential complications in the heterozygous patient.
The outcome of kidney transplantation sickle cell disease
In a study done by Nepat et al, using the data base of UNOS/OPTN, their conclusions were.
In a study done in London hospital by Joanna et al, involving 34 SCD recipients
How do you manage the transplantation
A) Pre-transplantation
B) Intraoperative
C) Post operative
Discuss immunosuppression
Most of the centres that has done SCD transplantation from US, UK and few done in some African countries use Basiliximab or ATG as an induction agent while the combination of CNI, MMF/Myfortic and prednisolone are used as a maintenance immunosuppressives. Most of the African countries rarely do steroid free as almost all their patient were maintained on low dose steroid like 5mg after one year post kidney transplantation.
Outcome in patient with sickle cell trait
The outcome of kidney transplantation in those with sickle cell trait is no different from those with other recipient without trait or the disease that had kidney transplantation using my centre in Nigeria experience (unpublished)
References
Very good lam sure your country has many information to share for SCD so does the Arab peninsula where cases are quite abundant.
Probably there is a higher incidence of living donors from the same family which makes us alert for the genotype AA is only accepted.
Outcome of renal transplantation in SCD:
Pre, intra, post-transplant management:
Immunosuppression:
SCT associated with better graft & patients survival ( comparable to recipients without SCR)
References:
Dear all some questions which you can meet during practice:
what are the needed vaccines prior to transplantation?
In aSCD transplanted patient what is the management of a SC crisi, vaso-occlusive and painful crisis.
What is the action of hydroxy urea and EBT during a crisis.
What is the outcome of kidney transplantation in sickle cell disease?
According to UNOS database study:
Lower patient and allograft survival in SCD kidney recipients when compared to non-SCD recipients (when the cause of ESRD is DM, glomerular disease, and HTN)
One year post transplant: insignificant patient survival (96% vs. 97%; p = 0.36). Significant death-censored graft survival (94% vs. 98%; p = 0.02)
Five-year post transplant: patient survival was comparable between the two groups (83% vs. 87%; p = 0.12). Death-censored graft survival in SCD was lower than in non-SCD recipients (71% vs. 89%; p < 0.001)
SCD patient and allograft outcomes in the recent era did not improve from the early era despite advances in kidney transplant care
How do you manage his transplantation (pre, intra and postoperative)?
Pretansplant management
Intensive work-up for surgery
Donor /recipient selection. Do donor genotype and exclude anyone with the abnormal sickle cell gene
Desensitization of high immunological risks
Vaccinations against S. pneumoniae, N. meningitidis, H. influenza type b, and influenza virus are strongly recommended at least 2 weeks before transplant surgery
Correction of anemia by erythropoietin (months prior to surgery) to limit the need of blood transfusion. For individuals who may require blood transfusion, delay for a period of 3 months and repeat the cross-matches
Optimal hydration
antimalarials
Peritransplant management
Patient preoperative Hb of 10g/Dl
Intraoperative monitoring of BP, cardiac rhythm, and oxygenation
Gentle dissection
Meticulous hemostasis
Antibiotic therapies and thromboprophylaxis
Morphine-based patient-controlled analgesia to avoid pain-induced crisis
Posttransplant management
Oral hydroxyurea (reduce incidents of crisis, acute chest syndrome, and mortality by up to 40%)
Exchange transfusions for sickling crises
Adequate fluid intake
Repiratory therapy
Regular clinic visits
Discuss immunosuppression?
SCD are usually high immunological risk (ATG)
Immunosuppression poses a potential challenge in curtailing infection after transplant. The following associated with optimal infection control:
1. Appropriate pre- and postexposure vaccination
2. Antibiotics
3. Strict safety precautions
4. Barrier nursing
5. Intensive postoperative management
6. Strict personal and environmental hygiene
7. Early therapeutic intervensions and infection control
Would it be different if he was heterozygous (trait)?
Patient with sickle cell trait also have high risk of complications but with a lesser degree than SCD
References
1. Leeaphorn N, Thongprayoon C, Vaitla P, Hansrivijit P, Jadlowiec CC, Mao SA, Chewcharat A, Katari S, Pattharanitima P, Boonpheng B, Kaewput W, Mao MA, Cooper M, Cheungpasitporn W. Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000-2019 UNOS/OPTN Database. J Clin Med. 2021 Jul 11;10(14):3063. doi: 10.3390/jcm10143063. PMID: 34300230; PMCID: PMC8305507.
2. Martin Igbokwe, Olalekan Olatise, Adegboyega Faponle, Abayomi Aremu, Vasanth Revanur, Habiba Jiwoh, 1 Omotola Obajolowo, and Idaomeh Ameh. Kidney Transplantation in Sickle Cell Disease Patients: Case Series and Experience from a Nigerian Kidney Transplant Center. Indian J Nephrol. 2022 Mar-Apr; 32(2): 164–167.
3. U. H. Okafor and E. Aneke, Outcome and challenges of kidney transplant in patients with sickle cell disease, Journal of Transplantation. Vol. 2013, Article ID 614610, 8 pages, 2013.
Thankyou well done
What are the high risk of complications in a sickle cell heterozygous person???
Thank you professor
Most people with SCT do not have symptoms but rarely they might develop complications of SCD (pain crises)
The patient is known to have sickle cell disease with sickle cell nephropathy and has had multiple crisis and multiple blood transfusions previously. His main triggering factor for crisis has been sepsis.
Outcome of kidney transplantation in SCD:
Studies have shown that SCD is associated with a lower patient survival (HR 2.87;95% CI 1.75-4.68) and death censored graft survival (HR 1.98;95% CI 1.30-3.01) compared to non-SCD recipients.
However, compared to SCD patients with ESKD on dialysis, SCD patients who were transplanted had significantly less mortality
Management of his transplantation:
Immunosuppression:
Patients with SCD have normally received multiple blood transfusions increasing their risk of allo-sensitization.
Therefore, patients with SCD should receive induction with ATG
Maintenance immunosuppression should include tacrolimus, mycophendlate and prednisolone
Would it be different if he was a heterozygous trait?
Patients who are heterozygous also have an increased risk of sickling although it is much less than the homozygous SCD patients. The outcomes are better post-transplant than homozygous SCD patients.
Thank you, Dr Hussein,
You did not mention what is the ideal level of HbS in this case and the role of exchange transfusion.
Thank you Professor Halawa
The ideal level of HbS should be less than 30%
Exchange transfusion can increase sensitization
Thank you, Hussein
Please see the ideal answer above
Outcome of kidney transplantation of SCD?
Retrospective study, ETB done in London;
Analysis of 2000-2019 using OPTN/UNOS database;
Kaplan-Meier;
10 years Kaplan-Meier 10 years estimate for dialysis, waitlisting, and post transplant mortality, which showed as 85%, 61%, and 50%, in sickle cell group respectively, compared to 81%, 41%, and 32% in the control groups.
Pre-Intra-Post Operative management of SCD kidney transplantation;
Pre-opearative ;
Intraoperative;
Post-operative;
Immunosuppressants;
All to ensur cahnce for minimum immunosuppressant as possible to minmize rate of infection, and sickle cell attack and crisis.
In SCT;
Refferences;
.
Dear Dr Kamal,
I enjoyed reading your informative write-up. Scientifically it is good.
Thank you, Dr Kamal,
You did not mention what is the ideal level of HbS in this case and the role of exchange transfusion
A 51-year-old Afro-Caribbean CK4 due to sickle cell nephropathy is known to be homozygous for sickle cell disease. He had many crises in the past triggered by sepsis and sometimes without any triggering event. He had many blood transfusions in the past. The last crisis was provoked following sepsis after an operation for priapism. He needs counselling for transplantation.
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What is the outcome of kidney transplantation in sickle cell disease?
Post-Transplant Outcomes between SCD vs. Non-SCD Recipients in Recent Era
Post-transplant outcomes were compared between SCD and other more prevalent causes of end-stage kidney disease.
——————————————————————————————————————-
How do you manage his transplantation (pre, intra and postoperative)?
The recommendations for perioperative management of kidney transplant in patients with SCD to enhance better outcome include the following:-
Sickle cell disease patients are predisposed to various haematological, cardiorespiratory, and immunological challenges.
——————————————————————————————————————-
Discuss immunosuppression?
——————————————————————————————————————–Would it be different if he was heterozygous (trait)?
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Reference
Dear Dr Wadi,
I enjoyed reading your informative write-up. Scientifically it is very good.
Ajay
Thanks alot Prof.Sharma
What is the outcome of kidney transplantation in sickle cell disease?
Compared to SCD patients on maintenance dialysis, the survival rate of people with SCD who have had a kidney transplant is higher. An analysis of the 2000–2019 UNOS/OPTN Database demonstrates that SCD recipients have a higher probability of graft failure and mortality compared to the control group. In one study, it was found that the 1-year survival of SCD patients receiving a transplant is 88%. Another study reported a 10-year survival in SCD ESRD patients receiving kidney transplants of 56% compared to only 14% in those receiving dialysis, and yet another study reported an increase in the 6-year survival of SCD renal transplant recipients from 56% in the era before 2000 to 70% from 2000-2011.
How do you manage his transplantation (pre, intra, and postoperatively)?
Treatment aims to optimize volume status, prevention of infections, prevention of sickle cell crisis, correction of anemia, and VTE prophylaxis.
Prevention of infection
Immunization before surgery is necessary since there is a possibility that vaccination will lose its efficacy after transplantation. Selecting the most compatible HLA donor will help to avoid using extensive immunosuppression, so that risk of infections is minimized.
Anemia management
There is no one set goal for the hemoglobin level in SCD patients who are receiving dialysis; however, some experts recommend aiming for 8-10 gm/dl if the HbS level is greater than 35% of the total hemoglobin in order to avoid hyperviscosity. The low target should be used in patients who experience frequent vaso-occlusive episodes, while the higher target should be used in patients who are only mildly affected or are asymptomatic or have other indications.
Iron should not be given routinely to these individuals since they typically have iron overload; rather, iron should only be given when iron stores are reduced or depleted. It is recommended to utilize blood that is antigen-matched whenever a blood transfusion is performed.
Fluid management
In patients who have sickle cell disease, there is a greater likelihood of metabolic acidosis and hyperkalemia, hence it is recommended that balanced solutions be used for fluid replacement rather than saline. During the intraoperative and postoperative periods, it is important to keep the patient’s volume status stable and to avoid volume depletion.
Pain control
Post-operative pain management is an absolute necessity, especially for patients with SCD. Pain management can be achieved by paracetamol or opiates. NSAIDs should not be used routinely in SCD.
VTE prophylaxis
Patients with SCD are at higher risk of thrombosis. It is important to prevent deep vein thrombosis, which is frequent in patients who have SCD F-immunosuppression, with perioperative and post-operative preventive anticoagulation.
Our patient in this clinical scenario is most likely highly sensitized from frequent blood transfusions. He may be placed on a waitlist for a considerable amount of time. Additionally, he may require aggressive immunosuppression with or without desensitization if he is transplanted to either an HLA or ABO incompatible recipient.
Hydroxyurea is the primary medication that is utilized in the treatment of SCD. This medication is advised in individuals who have experienced repeated vasoocclusive symptoms as well as in patients who have nephropathy due to the fact that it reduces proteinuria.
Discuss immunosuppression?
Because these patients have a greater risk of infection in comparison to recipients who do not have SCD, we have to select ABO compatible, best HLA matched donors using KPD in order to lessen the burden of immunosuppression and to make it possible to use steroid-free protocols whenever they are feasible.
The maintenance of stable hemoglobin, the preservation of oxygenated hemoglobin, and the elevation of fetal hemoglobin, typically by the use of hydroxyurea, are essential components of the management of sickle cell disease in patients. m-TOR inhibitors, which affect cellular development, proliferation, and survival, have been discovered to have an effect on boosting fetal hemoglobin, hence improving patient status and clinical outcomes. This effect is observed when m-TOR is combined with hydroxyurea.
Would it be different if he was heterozygous (trait)?
The difference lies in the fact that individuals with these characteristics only have a single mutated gene, meaning that they require fewer blood transfusions and, as a result, less sensitization.
The sickle cell trait is characterized by normal hemoglobin levels as well as an increased risk of thrombosis, urinary tract infections, and renal medullary cancer.
The short-term survival of transplant patients with sickle cell trait was equivalent to the survival of recipients of normal hemoglobin.
Hi Dr Habli,
I enjoyed reading your informative write-up. Scientifically it is good.
Ajay
What is the outcome of kidney transplantation in sickle cell disease?
Basically, Sickle cell nephropathy is a common presentation in patients with sickle cell disease. End-stage kidney disease is the most severe presentation of sickle cell nephropathy in terms of morbidity and mortality. Sickle cell disease or trait should not be regarded as a contraindication to transplantation, at least from the patient and allograft survival standpoint.
The outcome of kidney transplant in these SCD patients is variable. Earlier reports on kidney transplant in SCD patients suggested poor allograft survival. However, later studies have reported graft and patient survival rates comparable to those of nondiabetic patients with normal haemoglobin genotype. The one-year patient and graft survival of 87% and 67%, respectively.
How do you manage his transplantation (pre, intra and postoperative)?
The recommendations for perioperative management of kidney transplant in patients with SCD to enhance better outcome include the following:
-Ensure the operating and anesthesia teams are aware of the diagnosis of a sickle cell syndrome and the need for special attention in the patient.
-Ensure that patients preoperative haemoglobin of 10 g/dL is achieved by transfusion.
-Reduce hyperviscosity ,may be there is a need for exchanging blood transfusion.
-Minimize alloimmunization by giving antigen-matched blood.
-Preoperative monitoring of intake and output, hematocrit, peripheral perfusion, and oxygenation status.
-Intraoperative monitoring of blood pressure, cardiac rhythm and rate, and oxygenation.
-Intensive postoperative care including attention to hydration.
– Warming the graft with saline at 37°C, along with infusion of dopamine at 4 μg/kg/min during and after transplant, was advocated. Other suggestions include extra intravenous fluid to decrease blood viscosity, supplemental oxygen, and recombinant erythropoietin until auto production is sufficient.
– Adequate prophylactic measures including use of appropriate pre and postexposure vaccination, antibiotics, and strict safety precautions for optimal control of infection.
Discuss immunosuppression?
Suggested use of anti-lymphocyte globulin on induction, and use of hydroxyurea to increase HbF production in patients with homozygous sickle cell disease and it is significant role in reduction in painful crises.
Would it be different if he was heterozygous (trait)?
SCN had been reported to be far less frequent and severe in HbSC and HbAS than other phenotypes.
References:
W. H. Barber, M. H. Deierhol, B. A. Julian et al., “Renal transplantation in sickle cell anaemia and sickle cell trait,” Clinical Transplantation, vol. 1, pp. 169–175, 1987.
S. N. Chatterjee, “National study on natural history of renal allografts in sickle cell disease or trait,” Nephron, vol. 25, no. 4, pp. 199–201, 1980.
Dear Dr Fouad,
I enjoyed reading your informative write-up. Scientifically it is good.
Ajay
What is the outcome of kidney transplantation in sickle cell disease?
Overall outcome of patient and graft survival post KTX is better than remaining on hemodialysis.
One-year / Five-year death-censored graft survival in SCD were lower than in non-SCD recipients (1).
How do you manage his transplantation (pre, intra and postoperative)?
1-Our patient has had history of repeated blood transfusion which keep him liable for immunogenicity, so immunological work up should be carefully done to select good matched donor.
2-Data should be collected about steady-state hemoglobin and hematocrit, reticulocyte count, and WBC count, as well as history of blood transfusions and operating team and anesthetist must be aware about these data.
3-The severity of pre-existing cardiac and pulmonary complications of SCD need to be ascertained in the pre-operative assessment.
4- Preoperative monitoring of intake and output, hematocrit, peripheral perfusion, and oxygenation status to avoid dehydration status.
5-Achieve preoperative hemoglobin of 10 g/dL associated with no increase in perioperative complications.
6-To reduce hyper viscosity by exchanging blood transfusion
7-Anathetics should be aware about intraoperative monitoring of blood pressure, cardiac rhythm and rate, and oxygenation.
8-Laproscopic better than open to avoid long hospital stay and avoid post-operative complications.
9-Strict follow up of patients with stringent monitoring of patients wellbeing, renal function, drug level.
10- Postoperative Care as
a-pain control specially by opioids.
b- Maintaining adequate ventilation is the best preventive measure of acute chest syndrome.
c- Deep vein thrombosis prophylaxis.
d-Prophylaxis of any source of infection specially because functional a splenia in SCD patients is higher, with vaccination specially for encapsulated organisms.
Discuss immunosuppression?
We should select well matched donor to avoid heavy immunosuppressive , but induction as usual according to category of mismatching.
If low immunological risk ,try to use free steroid protocol .
Tacrolimus based therapy is the gold standard protocol .
Would it be different if he was heterozygous (trait)?
SCT is a benign carrier state , minor affection of renal system with good prognosis, less crisis and so less blood transfusion and less immunogenicity , with good outcome post KTX.
References:
1- Leeaphorn N, Thongprayoon C, Vaitla P, et al. Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000-2019 UNOS/OPTN Database. J Clin Med. 2021;10(14):3063. Published 2021 Jul 11. doi:10.3390/jcm10143063.
2- Adjepong KO, Otegbeye F, Adjepong YA. Perioperative Management of Sickle Cell Disease. Mediterr J Hematol Infect Dis. 2018;10(1):e2018032. Published 2018 May 1. doi:10.4084/MJHID.2018.032
3- Alhwiesh A. An update on sickle cell nephropathy. Saudi J Kidney Dis Transpl. 2014 Mar;25(2):249-65. doi: 10.4103/1319-2442.128495. PMID: 24625990.
Hi Dr Saad,
You mention, “but induction as usual according to category of mismatching”.
I would say that these patients are at a higher immunological risk due to repeated transfusions in past. Hence, usual induction may not be good enough.