Summary of this article:
Corticosteroids are important medication as immunosuppressive therapy in kidney transplantation but they have along chain of complication like DM ,HTN,dyslipidemia,osteoporosis ,a vascular necrosis,cataract and growth retardation in children.
in this article they discussed corticosteroids minimization vs avoidance in order to have a better outcome for both graft and patient ,
they discussed that via 3 strategies :
1-low Cs dose as maintenance therapy:dose: three daily IV pulses of MethylPrednisolone of 500 mg, 250 mg, and 250 mg.Tapered to MP 20 mg by week 2-4 and lastly to be tapered to 4 mg at 3 months.
results:lower rates of rejection with no difference on patient or graft surviaval
2- CS avoidance
It was conducted on low immunological risk patients and patients with potent induction therapy
Studies showed increased incidence of BPAR and some studies showed decreased incidence of DM and increased incidence of ATN
3-Cs withdrawal :
A-Early: One RCT reported more rejection in CS withdrawal 3-6 months after Transplantation
B-Late withdrawal :it is associated with high rate of rejection due to non compliance with no difference on graft survival but associated with side effects as side effects usually developes late.
In my center:
I will not use Cs avoidance but I can use early withdrawal especially in patients with comorbidities and in patients with low immunological risk and I would use this under umbrella of potent induction and maintainance immuosuppression.
Ben Lomatayo
3 years ago
Corticosteroids was introduced to renal transplantation since long time. It is known to have many side effects profiles. This study evaluated the cons and pro of CS minimization after kidney transplantation. CS minimization are either CS avoidance or CS withdrawal. CS withdrawal are classified to a) early first 3-6 months after Tx, b) late CS withdrawal after 6 months. Induction therapy and the use of CNI are pre-requisite for CS minimization, as well as low immunological risk patients. Studies on CS minimization revealed mixed result concerning cons and pros.
Low CS dose as maintenance therapy ; This strategy is associated with lower rejection rates. Patients and graft survival are not affected by CS minimisation in short-term but this is not clear over long-term. The results are not consistent regarding improvement in cardiovascular risk factors with CS minimization strategy.
CS avoidance ; The idea behind this is that , acute rejection is likely to happen easily with CS withdrawal following Tx (11). some studies showed higher acute rejection rate, and low rates of new onset diabetes after Tx. Laftava et. al. reported more interstitial fibrosis in protocol biopsies (13). It is not obvious if CS avoidance strategy to be shifted to CS maintenance strategy after treatment of acute rejection episodes. One retrospective study revealed that , lack of CS maintenance is a risk factor for acute rejection(18).
Early CS withdrawal ; This is now more feasible( TAC, MMF) than it was in the era of cyclosporine therapy. One RCT reported more rejection in CS withdrawal 3-6 months after Tx ( Vantrenterghem et al 21). Pascual et al (22), showed higher rejection rates but graft survival was not affected up to 3 years. It should be mentioned that induction immunosuppression was not used in these studies.
Late CS withdrawal ; This is less preferred than early CS withdrawal because some of the CS side effects usually occur in the first year(23). Another reason is increase rate of acute rejection after late CS withdrawal due to non-compliance(3). Patient and allograft survival was not affected at 2 years(24). Some studies demonstrated reduction in cardiovascular risk factors but these are observational studies and there is no RCT(25). Discussion ; CS withdrawal is not for high immunological risk and there is a concern that this can be a risk factor for post-transplant glomerulonephritis recurrence. Grenda et al (23), showed growth was enhance at 6 months by CS withdrawal. Elderly patients should not be included in CS minimization strategies due to acute rejection which is associated with poor graft outcomes. The cardiovascular benefits in elderly is controversial due short life span. CS minimization is also contraindicated in patients with DGF, and prolonged ischemia time. In conclusion, CS minimization is ideal for low immunological risk and it is not recommended in high risk patients, elderly, DGF, and prolonged cold ischemia time.
In my practice , I would consider CS minimization carefully in selected patient with close monitoring and follow up to avoid the cardiovascular & non-cardiovascular sides effects of CS.
Assafi Mohammed
3 years ago
Summary of the Article Corticosteroids have greater contribution as Immunosuppression in maintaining stability of kidney allograft function and in treating episodes of AR. Severe adverse effects of corticosteroids potentiated many researchers to evaluate strategies like minimization or withdrawal of corticosteroids in the post-transplant period. Adverse effects of CS:
Negative impact on cardiovascular: DM,HTN and Dyslipedaemia.
Non-Cardiovascular AEs: growth retardation, catarct,cosmotic stigma, osteoporosis and avascular necrosis.
CS Strategies (minimization or avoidance): 1.Low CS dose as maintenance therapy
Strategy aimed at three daily IV pulses of MethylPrednisolone of 500 mg, 250 mg, and 250 mg.Tapered to MP 20 mg by week 2-4 and lastly to be tapered to 4 mg at 3 months.
After 5 years follow-up: no difference in the rate of patient death, death-censored allograft loss and moderate/severe acute rejection.
BPAR was lower in CS continuation group.
2.CS avoidance
CS avoidance is selected for KTRs using potent induction immunosuppression and KTRs with low immunological risk.
BPAR rates were higher in CS avoidance and in regimens where CS were very early withdrawn.
3.CS withdrawal Early CS withdrawal:
CS-withdrawal under CsA-based regimen in maintenance therapy wasn’t successful.
Late CS withdrawal:
No difference in patient and allograft survival after a follow-up of 2 years.
Better patient and allograft survival after a follow-up of 7 years without significant difference in AR rate.
In my centre I will consider Challenges and opportunities of CS minimization strategies: Not suitable for :
Elderly because Because of their limited life span.
KTRs with delayed graft function (DGF).
KTRs with prolonged cold ischemia time.
Donation after cardiac death.
May be suitable in:
KTRs with low immunological risk.
KTRs at young age.
KTRs with very unlikely recurrence of GN.
RTX with use of potent induction therapy.
Heba Wagdy
3 years ago
Cs have several adverse events including cardiovascular disease risk factors as HTN, DM and dyslipidemia and other side effects as growth retardation, impaired wound healing, bone problems and cosmetic effects which may decrease patient’s compliance so several strategies are developed to allow CS minimization.
It may be through CS avoidance or withdrawal after transplant either early within 3-6 months post transplant or late 6 months post transplant.
the efficacy of CS minimization depends on immunosuppressive agents and immunological risk stratification.
results of studies on CS minimization were heterogenous and conflicting. CS minimization protocols include: low dose CS as maintenance therapy:
patient receives pulse solumedrol for 3 days intra and postoperative then rapid taper of CS till reach 4mg/day at 3 months and continue indefinitely in absence of AR.
A meta analysis showed that risk of AR was significantly increased with CS avoidance or withdrawal compared to maintenance CS with the same allograft survival, CS maintenance was associate with more occurrence of HTN, new onset DM and hypercholesterolemia CS avoidance:
It requires potent induction therapy and low immunological risk recipient
avoidance of induction therapy led to unacceptable high rate of AR.
A RCT compared early CS withdrawal versus CS continuation with the use of lymphocyte depleting agent and showed no difference in AR and allograft failure but the early CS withdrawal group was associated with increased fibrosis in protocol biopsies at 12 months.
Alemtuzumab may be used as CS sparing agent
A RCT compared Alemtuzumab induction without CS maintenance versus basiliximab induction with standard CS and showed that alemtuzumab regimen was associated with decreased BPAR at 6 months with the same patient and graft survival at 6 months Early CS withdrawal
It depends on maintenance therapy, cyclosporine based maintenance wasn’t successful.
Studies showed that early CS withdrawal didn’t affect patient and graft survival but was associated with more AR rates with no significant difference in adverse events Late CS withdrawal:
It is the least favorable method as certain complications already have happened and risk of AR increases on late withdrawal of immunosuppression. Challenges of CS minimization Not suitable for high immunological risk patients increase post transplant GN recurrence rate In elderly, AR rate is lower but more severe and have limited benefit from the decrease in cardiovascular risk due to their limited life span Inclusion criteria young transplant recipient (including children), first transplant, unsensitized to HLA antigens Exclusion criteria GN was the primary disease, perioperative ischemic insult to the graft, DGF, prolonged ischemia time, donation after cardiac death The preferred CS minimization strategy is either complete avoidance or very early withdrawal Induction with ATG or alemtuzumab is preferable with maintenance including CNI (tacrolimus)
Mohammed Sobair
3 years ago
Cs is important in transplant immunosuppression protocol, used to prevent acute
rejection, but its associate with wide plethora of side effect e.g. Hypertension, diabetes,
delayed wound healing, infection and bone disease (AVN, osteoporosis).
To eliminate this risk without causing rejection many type CS minimization is tried:
Low CS dose as maintenance therapy:
Where CS dose is reduced gradually in first three month to minimum and continue
indefinitely.
Astellas Corticosteroid Withdrawal Study, after a follow-up of 5 years, no difference was
found in the rate of patient death, death-censored allograft loss and moderate/severe
acute rejection. Total biopsy-confirmed acute rejection was lower in the CS continuation
arm (10.8% vs 17.8%, P = 0.04).
CS avoidance:
Requires the use of potent induction immunosuppression and the selection of low
immunological risk recipients.
A prospective RCT, which included 300 patients, compared very early CS withdrawal at
day 2 with standard CS. It also used basiliximab for induction, but maintenance was a
Calcineurin inhibitor and mycophenolate mofetil or Sirolimus. It found absolutely no
difference in patient and allograft survival, acute rejection, and incidence of CAN and
allograft function between the two arms at 3 years.
CS withdrawal:
Early CS withdrawal:
Overall, evidence about the benefit risk ratio of early CS withdrawal is weaker than that
of CS avoidance and follow-up times are shorter.
Late CS withdrawal:
It appears that late CS withdrawal (more than 6 mo. and possibly years after TX)
represents the least favorable method of the CS minimization strategies.
It is apparent that certain CS-related complications would already have been established
by that time.
Biopsy-proven acute rejection was manifested in 4% of CS withdrawal patient’s vs 1.4%
of controls (P > 0.05).
Patient and allograft survival was not different after a follow-up of 2 years.
Allograft function was also not different.
CS withdrawal resulted in reduced mean blood pressure but had no effect on other
metabolic risk factors.
Inclusion Criteria:
Young transplant recipient (including children).
Unsensitized to HLA alloantigen.
A primary disease that caused end-stage renal disease should not be
glomerulonephritis.
Exclusion:
Prolonged cold ischemia.
Donation after cardiac death.
DGF.
Elderly.
High risk patient.
Those with GN as cause of ESRD.
Conclusion:
Available data indicate that the preferred CS minimization strategy is probably either
complete CS avoidance or very early CS withdrawal. ATG (or Alemtuzumab may be
preferable to antiinterleukin-2 receptor monoclonal antibodies as induction agents in this
clinical scenario whereas maintenance immunosuppression should better contain the
Calcineurin inhibitor tacrolimus instead of cyclosporine.
Mujtaba Zuhair
3 years ago
Corticosteroids are important immunosuppressive drugs in renal transplantation , but prolonged use is associated with many side effects ( hypertension , DM , osteoporosis , cataract, … etc. ). so many attempts to use corticosteroid minimized immunosuppressive protocols had been proposed. The main concern with CS minimization is the increased incidence of acute rejection so nearly all the studies done in patients with low immunological risk
CS avoidance or CS very early withdrawal : to stop using steroids within less than 2 weeks post transplantation.
The use of basiliximab with CS avoidance is associated with higher degree of acute rejection but with similar degree of graft survival.
The use of lymphocyte depleting drugs with CS avoidance is associated with similar degree of acute rejection and graft survival but with higher degree of interstitial fibrosis.
Early CS withdrawal : to stop using steroids in less than 6 months after transplantation.
CS withdrawal with the use of cyclosporine and MMF was ineffective.
CS withdrawal with TAC and MMF is associated with higher acute rejections but with similar patient and graft survival .
Late CS withdrawal : to stop using CS after 6 months after transplantation.
The least favorable protocol of CS minimization since the side effects of CS maybe already happened.
Late CS withdrawal is associated with high acute rejection but with similar graft and patient survival.
Inclusion criteria :
first transplantation.
Low immunological risk (cPRA < 20%).
Primary disease is not GN.
Exclusion criteria :
DGF,
prolongrd cold ischemia time,
DCD donation.
Dalia Eltahir
3 years ago
Corticosteroid has been used since the beginning of kidney transplant. It has been associated with side effects like hypertension, diabetes mellitus, dyslipidemia, growth retardation, poor wound healing, osteoporosis, cataract . Many protocols done to minimize steroid use including either steroid avoidance (non-use or very early withdrawal – within 2 weeks) or steroid withdrawal (early: 3-6 month or late: more than 6 month). Steroid free associated with increased rates of acute rejection and reduce graft survival .Steroid minimization improved side effects of steroid . Steroid avoidance (and very early steroid withdrawal) regimes were associated with very high rates of acute rejection and increased interstitial fibrosis on protocol biopsies at 1 year in some studies while other studies showed no difference in acute rejection rates. There was no difference in graft and patient survival as well as graft function but post transplant diabetes mellitus was less frequent in the steroid avoidance group. Early steroid withdrawal associated with higher acute rejection rates but similar patient and graft survival at 3 years and lower total cholesterol and LDL levels. Late steroid withdrawal is also associated with increased rejection rates and similar graft function, patient and graft survival. Steroid minimization is not appropriate for patients with high immunological risk, elderly patients, transplant with increased cold ischemia time and DGF. How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)? inclusion . 1-A young transplant recipient (including children) who are un-sensitized and have low immunological risk .
2. The primary disease should not be glomerulonephritis.
3- Uncontrolled DM ,hypertension and obese patients
4. Maintenance immunosuppression should better contain tacrolimus . exclusion criteria 1- DGF 2. Prolonged cold ischemia time, 3- Donation after cardiac death. 4-high immunological risk . 5- Elderly
Hinda Hassan
3 years ago
1. Please summarise this article.
Steroid minimization is implemented to decrease side effects of them besides improving CVS risk factors. The involved strategies are:
(1) avoidance;
(2) early withdrawal ( 3-6 mo after Tx)
(3) late withdrawal (at least 6 mo after Tx).
The first and second approaches are associated with better outcomes in comparison with late withdrawal. But all of these are associated with high incidence of steroid sensitive acute rejection .
CS avoidance ,which include very early withdrawal at one week post-transplant ,showed comparable result to steroid continuation regarding the 5 year rate of patient death, death-censored allograft loss and moderate/severe acute rejection, Serum creatinine and creatinine clearance estimated by the Cockroft-Gault equation . But , the reduction in side effect was not different. Some studies revealed no differences regarding rejection and side effects. However all these studies confirmed the need for induction with a lymphocyte-depleting agent or alemtuzumab.
Early CS withdrawal: after 6 month follow up, acute rejection was more in the withdrawal arm during months 3-6 with reduction of only total cholesterol and LDL. Withdrawal in 3 and 6 months does not affect patient and allograft survival up to 3 years after Tx. But Total acute rejection rates were higher with early CS withdrawal .
Late CS withdrawal: this is the least popular strategy as rapid deterioration in osteoporosis occurs within the first year post transplant with increase in the acute rejection risk
Steroid minimization is beneficial in younger transplant recipients but in elderly it will increase the rate and severity of acute rejection without apparent reduction of cardiovascular disease risk factors .
Complete CS avoidance or very early CS withdrawal are better than late withdrawal. Acute rejection episodes associated with minimization strategies are considered mild , treatable and have no detrimental effects on patient survival, allograft survival or allograft function at a follow-up until 5 years.
2. How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
Inclusion criteria:
1. A young transplant recipient (including children) who are un-sensitized and have low immunological risk (primary transplant, low panel reactive antibodies) )
2. The primary disease should not be glomerulonephritis.
3. Induction with ATG (or alemtuzumab)
4. Maintenance immunosuppression should better contain tacrolimus instead of cyclosporine
Exclusion criteria:
1. DGF
2. Prolonged cold ischemia time,
Donation after cardiac death.
Amit Sharma
3 years ago
1. Please summarise this article.
Corticosteroid use has been associated since the beginning of kidney transplant. It has been associated with adverse effects like hypertension, diabetes mellitus, dyslipidemia, growth retardation, poor wound healing, osteoporosis, cataract etc. Hence various protocols have been formulated to minimize steroid use including either steroid avoidance (non-use or very early withdrawal – within 2 weeks) or steroid withdrawal (early: 3-6 month or late: more than 6 month).
Steroid free regimes have been shown to be associated with increased rates of acute rejection which patient and graft survival are similar to that with steroid based regimes.Steroid minimization has shown improved hypertension, diabetes mellitus and dyslipidemia occurrence.
Steroid avoidance (and very early steroid withdrawal) regimes were associated with very high rates of acute rejection (but mostly mild and easily treatable) and increased interstitial fibrosis on protocol biopsies at 1 year in some studies while other studies showed no difference in acute rejection rates. There was no difference in graft and patient survival as well as graft function but post transplant diabetes mellitus was less frequent in the steroid avoidance group.
Early steroid withdrawal has been shown to be associated with higher acute rejection rates but similar patient and graft survival at 3 years and lower total cholesterol and LDL levels. Late steroid withdrawal is also associated with increased rejection rates and similar graft function, patient and graft survival.
Steroid minimization is not appropriate for patients with high immunological risk, elderly patients, transplant with increased cold ischemia time and DGF. It has been shown that steroid avoidance (and very early steroid withdrawal) has better results than early steroid withdrawal while late steroid withdrawal has been associated with worst outcomes. Steroid minimization protocol implementation needs to be decided on the basis of individual characteristics of the transplant recipient.
2. How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
Corticosteroid minimization strategy can be utilized in a particluar subset of patients. These patients should undergo induction therapy with either ATG or Alemtuzumab and maintenance immunosuppression in form of Tacrolimus and MMF.
Inclusion criteria:
1) Young (including pediatric age group) patients
2) Low immunological risk
3) First transplant
4) Low PRA
5) Patient with contraindication to steroid use (like severe osteoporosis)
Exclusion criteria:
1) Severe DGF, severe peri-operative insult
2) Increased cold ischemia time
3) Elderly age group
4) Donation after cardiac death
5) Basic disease is glomerulonephritis
6) high immunological risk
Professor Ahmed Halawa
Admin
3 years ago
THANK YOU All FOR YOUR CONTRIBUTIONS
Mohamad Habli
3 years ago
For many decades, steroids were considered essential part of induction and maintenance immunosuppression in kidney transplantation. However, the chronic use of corticosteroids is associated with adverse events including osteoporosis, hyperglycemia, hypertension, hyperlipidemia, cosmotic side effects like hirsutism and many others. To overcome the side effects associated with steroid use in kidney transplantation, in particular cardiovascular adverse events, few protocols and suggestions of steroid free or low steroid regimens have been used.
The provided article reviewed studies on strategies for steroid minimization or avoidance:
(1) CS avoidance
(2) CS withdrawal:
1- Early withdrawal (usually 3-6 mo after Tx) OR
2- Late withdrawal (at least 6 mo after Tx).
(1) CS avoidance
Steroid avoidance strategies have been evaluated in few studies inclusing Basiliximab and antiyhmoglobulins as induction and CNI based maintenance in addition to MMF.
Basiliximab+EC-MPS+cyclosporins vs Basiliximab+EC-MPS+cyclosporins+ standard dose STEROIDS vs Basiliximab+EC-MPS+cyclosporins+ low dose STEROIDS, in low risk patients. Results showed significantly higher risk of rejection in the steroid avoidance group.
Another study evaluated induction with r-ALG followed by maintenance either tacrolimus/MMF/steroids vs tacrolimus/MMF. Results showed no difference in acute rejection and allograft with very early CS withdrawal at a follow-up time of 12 mo. However in the steroid free group, higher interstitial fibrosis rate was noted.
(2) CS withdrawal:
1- Early withdrawal (usually 3-6 mo after Tx): Results of the studies are heterogenous. . Pascual et al. reported that patient and graft survival are not affected by early CS withdrawal up to 3 years post transplant. Other study demonstrated higher acute rejection rate with early steroid withdrawal in patients treated with cyclosporine.
2- Late withdrawal (at least 6 mo after Tx). Results of this approach are not in favor of clinical use as it was associated with higher rate of rejection.
In RCT involving 212 patients, the incidence of biopsy proven acute rejection was found in 4% of CS withdrawal arm versus control arm. At 2 years follow up, patient and graft survival was not different between the 2 groups. No difference in allograft function. In CS withdrawal group no change in the metabolic profile.
How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
Corticosteroids(CS) are associated with many side effects ,so decrease of its use was thought about. Trials of avoidance or withdrawal had conflicting results in literature.
Maintenance therapy with low dose CS
either early CS withdrawal or low dose maintenance showed no difference in death rate, death censored graft los and moderate -severe rejection.
Avoidance of CS
Avoidance of CS needs induction with lymphocyte depleting agent to avoid risk of rejection.
Withdrawal of CS
Early withdrawal up to 3 years did not affect graft survival, with higher acute rejection in those treated with cyclosporine.
Late withdrawal of CS : BPAR was found in 4%and patient and graft survival not affected at 2 years of follow up. Also, allograft function was not affected.
2- CS minimization looks suitable in non sensitized ,young ,patients without ischemic heart and GN is not the primary disease. CS minimization should be avoided in case of DGF ,DCD and prolonged cold ischemia time
Uncontrolled DM& hypertension ,obesity ,osteoporosis ;generally low immunologic risk patients are situations that that regimen could be used and the reverse applies in case of high risk patients
Weam Elnazer
3 years ago
CS continue to be key component of the therapeutic armamentarium in renal transplantation. A push toward the exclusion of CS from immunosuppressive regimens throughout the induction and maintenance phases has evolved in order to decrease the plethora of negative effects associated with continuous CS usage. When compared to CS continuation, CS reduction techniques have resulted in a higher incidence of acute rejection than when CS is avoided. These acute rejection episodes, on the other hand, are considered modest and treatable with medication. Furthermore, they do not seem to have a negative impact on patient mortality, allograft survival, or allograft function when patients are followed for up to five years.
In spite of this, the observed tendency toward greater fibrosis is concerning, and it calls for the development of randomized controlled trials with longer follow-up to ascertain the real repercussions of CS reduction. The use of CS minimization protocols has been associated with a reduction in adverse effects (particularly improvement in dyslipidemia), but these findings have not always been reproducible, and it is unclear whether they could translate into a reduction in cardiovascular events in the clinical setting.
Achieving CS reduction cannot be suggested to all kidney transplant patients at this time, because of the limitations of technology.
different protocol:
Low dosage CS: CS maintenance as compared to CS avoidance. Induction using T cell depleting drugs or IL-2R blockers is standard. Five years of follow-up There was no difference in patient mortality, death censored graft loss or moderate/severe rejection in low dosage CS, however, CAN be higher in patients who avoided CS.
Avoiding CS increased the risk of rejection compared to receiving low dosage CS, and the rate of rejection was higher among non-induction recipients. After 12 months, the CS avoidance arm had greater interstitial fibrosis.
The risk of AR is higher in cyclosporine-based regimens, however, patients and graft survival did not vary after 3 years.
Late CS withdrawal: The least favourable regime due to steroid complications and significant risk of AR. The incidence of AR is high with the regime, although graft survival did not change after 2 years.
Finally, low dosage CS is the ideal IS method, although it may be tailored to certain recipient populations.
How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
I will avoid steroids in patients, including (0 mismatches, type 1 DM with a good HLA match. Exclusion: high immunological risk(poor HLA match, pretransplant DSA).
Huda Al-Taee
3 years ago
Corticosteroids (CS) has been included in IS regimens since the start of transplantation, but their use is associated with many side effects due to their non specific mechanism of action, so that efforts was made to minimize the exposure to these medications.
Strategies for CS minimization are:
CS avoidance
CS withdrawal ( early: within 3-6 months post transplant, late: at least 6 months post transplant).
there is overlap between these categories found in the literature.
The efficacy of CS minimization depends on the intensity of other IS medications and the immunological risk of the patient.
Data from CS minimization studies produced conflicting results, some studies showed a reduction in CV risk factors such as dyslipidemia, while others are not. some studies showed increased risk of rejection but no effect on graft survival.
So, the aim of this study was to identify the optimal management strategy which provide maximum benefit for different patients subsets and improve transplant outcome.
Low dose CS as maintenance therapy:
In the RCT with follow up period of 5 years, 386 patients assigned to either early CS withdrawal at one week post transplant or CS continuation with maintenance dose of 5mg/day at 6 months, there were no difference in the rate of death, death-censored graft loss and moderate-severe rejection.
CS avoidance:
Attempts to use CS avoidance regimens in the absence of induction IS resulted in a high rate of rejection. induction with lymphocyte depleting agents seems to be the optimal option for CS avoidance regimen without putting the patient at risk of rejection.
CS withdrawal
Early withdrawal:
In a systematic review involve 9 studies, 1820 patients the findings are:
patient and graft survival are not affected by early CS withdrawal up to 3 years post transplant.
Acute rejection rate was higher in patients treated with cyclosporine.
no significant difference was found for CV and non CV adverse events
induction IS was not used in any of the included studies.
Late CS withdrawal:
Represent the least favorable method of CS minimization.
In RCT involving 212 patients:
biopsy proven acute rejection was found in 4% of CS withdrawal arm versus control arm.
at 2 years follow up, patient and graft survival was not different between the 2 groups.
allograft function was not different
reduced BP in CS withdrawal group but no change in the metabolic profile.
Based on this evidence, patients who are suitable for CS minimization therapy are:
young
no prior transplant
non sensitized
the primary disease that caused ESRD should not be GN.
no perioperative ischemic event
contraindication to CS minimization:
DGF
prolonged cold ischemia time
DCD
Ban Mezher
3 years ago
CS is commonly used in IS regime, but it had several serious side effects as CV complications( TH, DM, & dyslipidemia) & non CV side effects ( growth retardation, poor worn healing, & bone complications). Due to wide range of CS side effects its tried to minimizing the exposure to it in recipients with stable renal function. CS minimization can be classified into:
CS avoidance
CS withdrawal ( early in first 3-6 months or late after 6 months post transplantation).
Several trials study the CS minimization regimes benefit & harm but the result had heterogeneity. Some of these trial show reduce in CV risk factors( hyperlipidemia) without proven benefit in reducing CV disease purden.
Aim of this study is to find an appropriate treatment strategy that maximizing benefits in different patients subsets with out increase risk of graft loss.
Low dose CS: using low CS as maintenance were studies in comparison to CS avoidance. All recipients receive induction with T cell depleting agents or IL-2R blocker. The patients followed for 5 years. The result show that there was no difference in patients death, death censored graft loss & moderate/ severe rejection in low dose CS, but it was found that CAN was more among patients with CS avoidance regime.
CS avoidance: It shown that risk of rejection increased in patients with CS avoidance regime when compared with patients receive low dose CS, & the incidence of rejection was more among recipients not receive induction. Graft survival not different 12 months of follow-up but interstitial fibrosis was more in CS avoidance arm.
Early CS withdrawal: It was found that the risk of AR is more in cyclosporine based regime but patients & graft survival didn’t differ after 3 years of follow-up.
Late CS withdrawal: Its the least favorable regime because steroid complication established by this period & the risk of AR was high in this period. It was found that incidence of AR is high with regime but graft survival didn’t differ during 2 years follow-up.
In conclusion low dose CS is the best IS strategy, but CS minimized regime can be offered for special recipients subgroups.
In my center I prefer to use low dose CS, but can use CS avoidance regime in some patients :
Inclusion criteria : first transplantation , no history of sensitization, young, severe osteoporosis
Exclusion criteria : high immunological risk, elderly , GN as primary disease
Abdulrahman Ishag
3 years ago
Please summarise this article.
Although corticosteroids are corner store in induction and maintenance immuuno suppression protocols ,their side effects negatively impact patient compliance .these side effect include hypertension ,diabetes , dyslipidaemia , growth retardation impaired wound healing ,cataract , bone problem and cosmetic effects .minimizing the exposure to corticosteroids in transplant recipients with stable allograft has been manifested by renal transplant clinicians to reduce their associated side effects .
The strategies for corticosteroids minimization are;
1-coricosteroids withdrawal following a period after transplantation
-very early withdrawal (less than 2 weeks ) has been classified under both CS avoidance and withdrawal .
-early withdrawal ;usually 3-6 months after transplantation .
-late withdrawal ; at least 6 months after transplantation .
2- corticosteroids avoidance
3- low dose corticosteroids maintenance therapy
Safe application of CS minimization required ;
-induction immunosuppression
-calcinurin maintenance therapy
-patient at low immunological risk are considered as ideal candidate for the implementation for CS minimization .
Low CS dose as maintenance therapy ;
acute rejection rates are constantly lower when CS maintenance regimens are used. Patient and allograft survival seems not to be influenced by CS minimization, but it is unknown if this remains the same with longer follow-up. chronic allograft nephropathy (CAN) incidence at 5 years was more than double with very early CS withdrawal compared to a continuation. Although CS minimization may permit some improvement in cardiovascular risk factors, data are not consistent about it. As far as it concerns non cardiovascular adverse events, very early CS withdrawal reduced bone fractures and a vascular necrosis but it was paradoxically associated with more frequent sub capsular cataract.
CS avoidance ;
induction with lymphocyte depleting agents seems to be the optimal option for consolidating the benefits of CS avoidance strategies without putting renal allograft at risk of acute rejection. A beneficial effect of very early CS withdrawal was shown for new onset diabetes mellitus, sub capsular cataract, and a vascular necrosis. Studies found no difference in patient and allograft survival, acute rejection, incidence of CAN and allograft function between the two arms at 3 years. A lower frequency of new-onset diabetes mellitus was noted in the very early CS withdrawal group.
Early CS withdrawal ;
It is unknown if induction with lymphocyte depleting agents or antiinterleukin-2 receptor monoclonal antibodies were used in any of the studies, it would have any meaningful impact on the results. Overall, evidence about the benefit risk ratio of early CS withdrawal is weaker than that of CS avoidance and follow-up times are shorter. Although reduction of total cholesterol levels was observed with early CS withdrawal, no significant difference was found for any of the other cardiovascular or non-cardiovascular adverse events. Late CS withdrawal ;
It is apparent that certain CS-related complications would already have been established by that time. it is well known that a rapid deterioration in osteoporosis occurs within the first post transplant year. Moreover, acute rejection risk is clearly increased upon late withdrawal of immune suppressantsas dictated by cases of non-compliant patients. CS withdrawal resulted in reduced mean blood pressure but had no effect on other metabolic risk factors. The reduction was also noted in the incidence of cardiovascular parameters. patient and allograft survival was better in late CS withdrawal . In conclusion;
Although corticosteroids have been traditional components of immunosuppressive regimens in renal transplantation, corticosteroid minimization strategies are developed in an attempt to mitigate their many side effects. The benefit from this approach must be balanced against the risk of acute rejection due to insufficient immune suppression and the potential harm to allograft survival. Patient selection according to the immunological risk and the induction immunosuppression is the principal factors that determine the success of corticosteroid withdrawal and avoidance protocols.
How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
Inclusion criteria ;
Low immunological risk patient with or at risk of the following;
-Obesity
-Osteoporosis
-Diabetes , hypertension , dyslipidaemia
-Cardiovascular disease
-Cosmotic side effects of steroids.
Exclusion criteria
High immunological risk
Absence of metabolic indication
exclusion criteria
high immunological risk
patient at risk of recurrence GN
Doaa Elwasly
3 years ago
1. Please summarise this article.
Corticosteroid minimization strategies are established to avoid steroids sideeffects. A balance must be made between the risk of acute rejection and their side effects. Methodolgy
The corticosteroids minimization strategies are either avoidance ( very early withdrawal )or withdrawal after a period of transplantation which could be either early (3-6 months post transplantation )or late withdrawal ( after 6 months from transplantation)
Low immunological risk cases are more suitable to apply this regimen
Induction immunosuppression is needed and maintenance therapy involving calcineurin inhibitors is the safe protocol to apply this regimen .
The aim of this study is to reach the best management protocol, without compromising safety and improving Tx net results. RESULTS
–Low CS dose as maintenance therapy
In a RCT they compared 2 groups one with corticosteroid withdrawal 1 week post transplantation and the other tappering it to 5 mg at 6 months.
Induction immunosuppression with ATG or basiliximab and maintenance with tacrolimus and MMF were given.
After 5 y follow up period there was no difference in patient survival ,acute rejection and GFR but biopsy-confirmed acute rejection was less in the CS continuation group and in ATG induction group but was not statically significant in the latter .
Chronic allograft nephropathy was higher in early withdrawal group
Follow up for longer times till 10 y is needed to justify the results
–CS avoidance
A multicenter RCT used basiliximab for induction and maintenance with cyclosporine and MMF compared no CS to CS withdrawal by day 7 to standard CS.
BPAR was higher with CS avoidance and withdrawal groups and no difference was noted regarding e GFR , patient and allograft survival.
Multiple other studies used other induction and maintenance choices and concluded the same previous results
Meanwhile induction with lymphocyte depleting agents as lately used alemtuzumab seems the best choice for preserving CS avoidance strategies privileges without risking the allograft.
–CS withdrawal
· Early CS withdrawal:
Cyclosporine use as maintenance wasnot possible but Tac and MMF usage enabled reapplying this strategy.
Multiple studies demonstrated that patient and allograft survival till 3 years after Tx is not affected by early Cs withdrawal ,but induction therapy wasnot used in those studies
· Late CS withdrawal:
Is less prefered strategy as after 6 months already CS side effects had occurred and graft is liable for late rejection.
A study concluded that patient and allograft survival was better than retrospectively matched controls over a follow up time of 7 years with no difference in acute rejection rates for patients with CS withdrawal more than 6 mo from Tx Discussion
The favorable effects of CNS minimization protocol in low immunological risk cases encouraged using it with high risk cases as well.
This strategy was of special interest particularly in pediatric group to avoid side effects involving growth retardation,etc
On the other hand this protocol disadvantage is the high rate of post transplant GN recurrence .
This protocol is not suitable for elderly although they have lower rate of acute rejection but it is more severe if occurred.
2-How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
-Inclusion criteria
Low imunological risk as first transplant ,
<20% PRA,
unsensitized to HLA antigens,
low risk of GN recurrence
Young patients
-Exclusion criteria
High immunological risk as multiple transplant , multiparus ,
blood transfusion
highly sensitized cases
Elderly population
Transplant recipients with delayed graft function (DGF) and prolonged cold ischemia time and patient receiving a graft from a donor post cardiac arrest
Riham Marzouk
3 years ago
Steroid minimization protocol
Aim to decrease the incidence of complications like cardiovascular comorbidities , HTN, DM, bone disease like osteoporosis, also cosmetic disfigurement will leads to non compliance to medications and psychological issues which in turn predispose to acute rejection or CAN.
Benefits against risks of under immunosuppression should be considered, because of the risk of steroid sensitive acute rejection, which will affect graft outcome.
Steroid minimization can be divided into :
1- Steroid avoidance or very early withdrawal less than 2 weeks post-transplant
2- Steroid withdrawal which can be very early less than 2 weeks post-transplant, early less than 6 months post-transplant or late after 6 months post-transplant.
The ideal candidate for CS minimization protocol is immunological low risk patients who are non-sensitized, and should be first transplant, and their original disease should be non-GN. Also induction should be given and CNI should be included in the protocol.
Early withdrawal should be done to get maximum benefits from avoidance or withdrawal of steroid
CS still an important agent of the immunosuppression protocol in renal transplantation.
CS elimination from induction and maintenance immunosuppression regimens has developed to reduce its side effects associated with chronic CS use.
CS minimization strategies have resulted in an increased incidence of acute rejection compared to CS continuation.
steroid minimization protocol in my practice is not well defined except when there is dramatic complications
Sherif Yusuf
3 years ago
Corticosteroids are considered the cornerstone of immune suppression in renal transplantation. It is used in induction protocols, an important member of triple maintenance immunosuppressive therapy recommended for most renal transplant patients and it is considered to be a key component in the treatment of rejection.
Side effects of glucocorticoids
Osteopenia, osteoporosis, increased risk of skeletal fractures and AVN
Worsening of DM or increase in the risk of PTDM
Hypertension
Obesity
Alteration of lipid metabolism with subsequent increase in the incidence of atherosclerosis
Delayed wound healing
Cosmetic problems including steroid acne, hirsutism
Increase risk of cataract
Because of the side effects of corticosteroids, there are many trials on corticosteroid minimization which include one of the following protocols:
1. Complete withdrawal which can be done either early within 3- 6 months after transplantation or late after 1 year.
2. Complete avoidance from the start
Possible drawbacks in the use of corticosteroid minimization protocols
Increase risk of acute rejection
Recurrence of primary disease
Glucocorticoid minimization should not be initiated in the following patients (exclusion criteria):
Patients with DGF due to very high risk of acute rejection
Patients with graft dysfunction
High immunological risk patients including those with re-transplantation or with PRA > 20 %
African American since the rate of acute rejection is higher in this type of patients
Elderly patients since acute rejection in this group may be more severe and decrease survival; moreover cardiovascular side effects may be not significant due to limited life expectancy.
Patients with possible recurrence of glomerulonephritis
Precautions in the use of CS minimization protocol (inclusion criteria):
Corticosteroid withdrawal can be started in low or intermediate risk, young, non-African American patients
If there are side effects of corticosteroids or anticipation of bad outcome due to CS side effects
Stable renal function
The cause of the primary disease is not glomerulonephritis with known recurrence after transplantation
Using tacrolimus based immunosuppressive protocol
If late corticosteroid withdrawal is planned there should be no episode of acute rejection in the past 6-12 months.
Patients that are a candidate for corticosteroid avoidance and early glucocorticoid withdrawal < 6 months post-transplantation should receive CNI (better tacrolimus), MMF, and a polyclonal antibody induction
Please summarise this article. Side effects of corticosteroid are –
hypertension
diabetes mellitus
dyslipidemia
growth retardation
impaired wound healing
subcapsular cataract
bone problems (osteoporosis, fractures, avascular necrosis)
cosmetic effects Strategies for CS minimization can be categorized as:
(1) CS avoidance;
(2) CS withdrawal following a period after Tx. further divided as early withdrawal (weeks or months after Tx, usually 3-6 mo after Tx) or late withdrawal (at least 6 mo after Tx). CS avoidance-
In the Astellas Corticosteroid Withdrawal Study), Woodle et al assigned 386 renal transplant recipients with PRA (panel reactive <25%) to very early CS withdrawal at 1 week post-transplant or CS continuation tapered to 5 mg prednisolone per day at 6 month.
induction immunosuppression-
68% of them with the lymphocyte-depleting agent anti-thymocyte
globulin (ATG)
32% with anti-interleukin-2 receptor monoclonal antibodies.
Maintenance immunosuppressive-
tacrolimus and mycophenolate mofetil (MMF).
After a follow-up of 5 years-
no difference was found in
the rate of patient death
death-censored allograft loss
moderate/severe acute rejection.
biopsy-proven acute rejection rates were numerically lower with ATG induction than
with anti-interleukin-2 receptor monoclonal antibodies in very early CS withdrawal patients.
Serum creatinine and creatinine clearance were similar between the two arms at 5 years.
chronic allograft nephropathy (CAN) incidence at 5 years was more than double in the early CS withdrawal arm.
Early CS withdrawal-
Patient and allograft survival is not affected by early Cs withdrawal up to 3 years after Tx. Total acute rejection rates were higher with early CS withdrawal in cyclosporine-treated patients. no significant difference was found for any of the other cardiovascular or non-cardiovascular adverse events. It is worth mentioning that induction immunosuppression was not used in any of the studies. Late CS withdrawal:
It appears that late CS withdrawal (more than 6 mo and possibly years after Tx) represents
the least favorable method of the CS minimization strategies.
In contrast to the perceived benefits of CS minimization in younger transplant recipients, this strategy may not be suitable for elderly patients.
CS minimization may not also be suitable for transplant recipients with delayed graft function
(DGF) and prolonged cold ischemia time.
How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)? INCLUSION –
Paediatric patient non sensitised.
Summary of this article:
Corticosteroids are important medication as immunosuppressive therapy in kidney transplantation but they have along chain of complication like DM ,HTN,dyslipidemia,osteoporosis ,a vascular necrosis,cataract and growth retardation in children.
in this article they discussed corticosteroids minimization vs avoidance in order to have a better outcome for both graft and patient ,
they discussed that via 3 strategies :
1-low Cs dose as maintenance therapy:dose: three daily IV pulses of MethylPrednisolone of 500 mg, 250 mg, and 250 mg.Tapered to MP 20 mg by week 2-4 and lastly to be tapered to 4 mg at 3 months.
results:lower rates of rejection with no difference on patient or graft surviaval
2- CS avoidance
It was conducted on low immunological risk patients and patients with potent induction therapy
Studies showed increased incidence of BPAR and some studies showed decreased incidence of DM and increased incidence of ATN
3-Cs withdrawal :
A-Early: One RCT reported more rejection in CS withdrawal 3-6 months after Transplantation
B-Late withdrawal :it is associated with high rate of rejection due to non compliance with no difference on graft survival but associated with side effects as side effects usually developes late.
In my center:
I will not use Cs avoidance but I can use early withdrawal especially in patients with comorbidities and in patients with low immunological risk and I would use this under umbrella of potent induction and maintainance immuosuppression.
Corticosteroids was introduced to renal transplantation since long time. It is known to have many side effects profiles. This study evaluated the cons and pro of CS minimization after kidney transplantation. CS minimization are either CS avoidance or CS withdrawal. CS withdrawal are classified to a) early first 3-6 months after Tx, b) late CS withdrawal after 6 months. Induction therapy and the use of CNI are pre-requisite for CS minimization, as well as low immunological risk patients. Studies on CS minimization revealed mixed result concerning cons and pros.
Summary of the Article
Corticosteroids have greater contribution as Immunosuppression in maintaining stability of kidney allograft function and in treating episodes of AR. Severe adverse effects of corticosteroids potentiated many researchers to evaluate strategies like minimization or withdrawal of corticosteroids in the post-transplant period.
Adverse effects of CS:
CS Strategies (minimization or avoidance):
1.Low CS dose as maintenance therapy
2.CS avoidance
3.CS withdrawal
Early CS withdrawal:
Late CS withdrawal:
In my centre I will consider Challenges and opportunities of CS minimization strategies:
Not suitable for :
May be suitable in:
Cs have several adverse events including cardiovascular disease risk factors as HTN, DM and dyslipidemia and other side effects as growth retardation, impaired wound healing, bone problems and cosmetic effects which may decrease patient’s compliance so several strategies are developed to allow CS minimization.
It may be through CS avoidance or withdrawal after transplant either early within 3-6 months post transplant or late 6 months post transplant.
the efficacy of CS minimization depends on immunosuppressive agents and immunological risk stratification.
results of studies on CS minimization were heterogenous and conflicting.
CS minimization protocols include:
low dose CS as maintenance therapy:
patient receives pulse solumedrol for 3 days intra and postoperative then rapid taper of CS till reach 4mg/day at 3 months and continue indefinitely in absence of AR.
A meta analysis showed that risk of AR was significantly increased with CS avoidance or withdrawal compared to maintenance CS with the same allograft survival, CS maintenance was associate with more occurrence of HTN, new onset DM and hypercholesterolemia
CS avoidance:
It requires potent induction therapy and low immunological risk recipient
avoidance of induction therapy led to unacceptable high rate of AR.
A RCT compared early CS withdrawal versus CS continuation with the use of lymphocyte depleting agent and showed no difference in AR and allograft failure but the early CS withdrawal group was associated with increased fibrosis in protocol biopsies at 12 months.
Alemtuzumab may be used as CS sparing agent
A RCT compared Alemtuzumab induction without CS maintenance versus basiliximab induction with standard CS and showed that alemtuzumab regimen was associated with decreased BPAR at 6 months with the same patient and graft survival at 6 months
Early CS withdrawal
It depends on maintenance therapy, cyclosporine based maintenance wasn’t successful.
Studies showed that early CS withdrawal didn’t affect patient and graft survival but was associated with more AR rates with no significant difference in adverse events
Late CS withdrawal:
It is the least favorable method as certain complications already have happened and risk of AR increases on late withdrawal of immunosuppression.
Challenges of CS minimization
Not suitable for high immunological risk patients
increase post transplant GN recurrence rate
In elderly, AR rate is lower but more severe and have limited benefit from the decrease in cardiovascular risk due to their limited life span
Inclusion criteria
young transplant recipient (including children), first transplant, unsensitized to HLA antigens
Exclusion criteria
GN was the primary disease, perioperative ischemic insult to the graft, DGF, prolonged ischemia time, donation after cardiac death
The preferred CS minimization strategy is either complete avoidance or very early withdrawal
Induction with ATG or alemtuzumab is preferable with maintenance including CNI (tacrolimus)
Cs is important in transplant immunosuppression protocol, used to prevent acute
rejection, but its associate with wide plethora of side effect e.g. Hypertension, diabetes,
delayed wound healing, infection and bone disease (AVN, osteoporosis).
To eliminate this risk without causing rejection many type CS minimization is tried:
Low CS dose as maintenance therapy:
Where CS dose is reduced gradually in first three month to minimum and continue
indefinitely.
Astellas Corticosteroid Withdrawal Study, after a follow-up of 5 years, no difference was
found in the rate of patient death, death-censored allograft loss and moderate/severe
acute rejection. Total biopsy-confirmed acute rejection was lower in the CS continuation
arm (10.8% vs 17.8%, P = 0.04).
CS avoidance:
Requires the use of potent induction immunosuppression and the selection of low
immunological risk recipients.
A prospective RCT, which included 300 patients, compared very early CS withdrawal at
day 2 with standard CS. It also used basiliximab for induction, but maintenance was a
Calcineurin inhibitor and mycophenolate mofetil or Sirolimus. It found absolutely no
difference in patient and allograft survival, acute rejection, and incidence of CAN and
allograft function between the two arms at 3 years.
CS withdrawal:
Early CS withdrawal:
Overall, evidence about the benefit risk ratio of early CS withdrawal is weaker than that
of CS avoidance and follow-up times are shorter.
Late CS withdrawal:
It appears that late CS withdrawal (more than 6 mo. and possibly years after TX)
represents the least favorable method of the CS minimization strategies.
It is apparent that certain CS-related complications would already have been established
by that time.
Biopsy-proven acute rejection was manifested in 4% of CS withdrawal patient’s vs 1.4%
of controls (P > 0.05).
Patient and allograft survival was not different after a follow-up of 2 years.
Allograft function was also not different.
CS withdrawal resulted in reduced mean blood pressure but had no effect on other
metabolic risk factors.
Inclusion Criteria:
Young transplant recipient (including children).
Unsensitized to HLA alloantigen.
A primary disease that caused end-stage renal disease should not be
glomerulonephritis.
Exclusion:
Prolonged cold ischemia.
Donation after cardiac death.
DGF.
Elderly.
High risk patient.
Those with GN as cause of ESRD.
Conclusion:
Available data indicate that the preferred CS minimization strategy is probably either
complete CS avoidance or very early CS withdrawal. ATG (or Alemtuzumab may be
preferable to antiinterleukin-2 receptor monoclonal antibodies as induction agents in this
clinical scenario whereas maintenance immunosuppression should better contain the
Calcineurin inhibitor tacrolimus instead of cyclosporine.
Corticosteroids are important immunosuppressive drugs in renal transplantation , but prolonged use is associated with many side effects ( hypertension , DM , osteoporosis , cataract, … etc. ). so many attempts to use corticosteroid minimized immunosuppressive protocols had been proposed. The main concern with CS minimization is the increased incidence of acute rejection so nearly all the studies done in patients with low immunological risk
CS avoidance or CS very early withdrawal : to stop using steroids within less than 2 weeks post transplantation.
The use of basiliximab with CS avoidance is associated with higher degree of acute rejection but with similar degree of graft survival.
The use of lymphocyte depleting drugs with CS avoidance is associated with similar degree of acute rejection and graft survival but with higher degree of interstitial fibrosis.
Early CS withdrawal : to stop using steroids in less than 6 months after transplantation.
CS withdrawal with the use of cyclosporine and MMF was ineffective.
CS withdrawal with TAC and MMF is associated with higher acute rejections but with similar patient and graft survival .
Late CS withdrawal : to stop using CS after 6 months after transplantation.
The least favorable protocol of CS minimization since the side effects of CS maybe already happened.
Late CS withdrawal is associated with high acute rejection but with similar graft and patient survival.
Inclusion criteria :
Exclusion criteria :
Corticosteroid has been used since the beginning of kidney transplant. It has been associated with side effects like hypertension, diabetes mellitus, dyslipidemia, growth retardation, poor wound healing, osteoporosis, cataract . Many protocols done to minimize steroid use including either steroid avoidance (non-use or very early withdrawal – within 2 weeks) or steroid withdrawal (early: 3-6 month or late: more than 6 month).
Steroid free associated with increased rates of acute rejection and reduce graft survival .Steroid minimization improved side effects of steroid .
Steroid avoidance (and very early steroid withdrawal) regimes were associated with very high rates of acute rejection and increased interstitial fibrosis on protocol biopsies at 1 year in some studies while other studies showed no difference in acute rejection rates. There was no difference in graft and patient survival as well as graft function but post transplant diabetes mellitus was less frequent in the steroid avoidance group.
Early steroid withdrawal associated with higher acute rejection rates but similar patient and graft survival at 3 years and lower total cholesterol and LDL levels. Late steroid withdrawal is also associated with increased rejection rates and similar graft function, patient and graft survival.
Steroid minimization is not appropriate for patients with high immunological risk, elderly patients, transplant with increased cold ischemia time and DGF.
How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)? inclusion .
1-A young transplant recipient (including children) who are un-sensitized and have low immunological risk .
2. The primary disease should not be glomerulonephritis.
3- Uncontrolled DM ,hypertension and obese patients
4. Maintenance immunosuppression should better contain tacrolimus .
exclusion criteria
1- DGF
2. Prolonged cold ischemia time,
3- Donation after cardiac death.
4-high immunological risk .
5- Elderly
1. Please summarise this article.
Steroid minimization is implemented to decrease side effects of them besides improving CVS risk factors. The involved strategies are:
(1) avoidance;
(2) early withdrawal ( 3-6 mo after Tx)
(3) late withdrawal (at least 6 mo after Tx).
The first and second approaches are associated with better outcomes in comparison with late withdrawal. But all of these are associated with high incidence of steroid sensitive acute rejection .
CS avoidance ,which include very early withdrawal at one week post-transplant ,showed comparable result to steroid continuation regarding the 5 year rate of patient death, death-censored allograft loss and moderate/severe acute rejection, Serum creatinine and creatinine clearance estimated by the Cockroft-Gault equation . But , the reduction in side effect was not different. Some studies revealed no differences regarding rejection and side effects. However all these studies confirmed the need for induction with a lymphocyte-depleting agent or alemtuzumab.
Early CS withdrawal: after 6 month follow up, acute rejection was more in the withdrawal arm during months 3-6 with reduction of only total cholesterol and LDL. Withdrawal in 3 and 6 months does not affect patient and allograft survival up to 3 years after Tx. But Total acute rejection rates were higher with early CS withdrawal .
Late CS withdrawal: this is the least popular strategy as rapid deterioration in osteoporosis occurs within the first year post transplant with increase in the acute rejection risk
Steroid minimization is beneficial in younger transplant recipients but in elderly it will increase the rate and severity of acute rejection without apparent reduction of cardiovascular disease risk factors .
Complete CS avoidance or very early CS withdrawal are better than late withdrawal. Acute rejection episodes associated with minimization strategies are considered mild , treatable and have no detrimental effects on patient survival, allograft survival or allograft function at a follow-up until 5 years.
2. How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
Inclusion criteria:
1. A young transplant recipient (including children) who are un-sensitized and have low immunological risk (primary transplant, low panel reactive antibodies) )
2. The primary disease should not be glomerulonephritis.
3. Induction with ATG (or alemtuzumab)
4. Maintenance immunosuppression should better contain tacrolimus instead of cyclosporine
Exclusion criteria:
1. DGF
2. Prolonged cold ischemia time,
Donation after cardiac death.
1. Please summarise this article.
Corticosteroid use has been associated since the beginning of kidney transplant. It has been associated with adverse effects like hypertension, diabetes mellitus, dyslipidemia, growth retardation, poor wound healing, osteoporosis, cataract etc. Hence various protocols have been formulated to minimize steroid use including either steroid avoidance (non-use or very early withdrawal – within 2 weeks) or steroid withdrawal (early: 3-6 month or late: more than 6 month).
Steroid free regimes have been shown to be associated with increased rates of acute rejection which patient and graft survival are similar to that with steroid based regimes.Steroid minimization has shown improved hypertension, diabetes mellitus and dyslipidemia occurrence.
Steroid avoidance (and very early steroid withdrawal) regimes were associated with very high rates of acute rejection (but mostly mild and easily treatable) and increased interstitial fibrosis on protocol biopsies at 1 year in some studies while other studies showed no difference in acute rejection rates. There was no difference in graft and patient survival as well as graft function but post transplant diabetes mellitus was less frequent in the steroid avoidance group.
Early steroid withdrawal has been shown to be associated with higher acute rejection rates but similar patient and graft survival at 3 years and lower total cholesterol and LDL levels. Late steroid withdrawal is also associated with increased rejection rates and similar graft function, patient and graft survival.
Steroid minimization is not appropriate for patients with high immunological risk, elderly patients, transplant with increased cold ischemia time and DGF. It has been shown that steroid avoidance (and very early steroid withdrawal) has better results than early steroid withdrawal while late steroid withdrawal has been associated with worst outcomes. Steroid minimization protocol implementation needs to be decided on the basis of individual characteristics of the transplant recipient.
2. How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
Corticosteroid minimization strategy can be utilized in a particluar subset of patients. These patients should undergo induction therapy with either ATG or Alemtuzumab and maintenance immunosuppression in form of Tacrolimus and MMF.
Inclusion criteria:
1) Young (including pediatric age group) patients
2) Low immunological risk
3) First transplant
4) Low PRA
5) Patient with contraindication to steroid use (like severe osteoporosis)
Exclusion criteria:
1) Severe DGF, severe peri-operative insult
2) Increased cold ischemia time
3) Elderly age group
4) Donation after cardiac death
5) Basic disease is glomerulonephritis
6) high immunological risk
THANK YOU All FOR YOUR CONTRIBUTIONS
For many decades, steroids were considered essential part of induction and maintenance immunosuppression in kidney transplantation. However, the chronic use of corticosteroids is associated with adverse events including osteoporosis, hyperglycemia, hypertension, hyperlipidemia, cosmotic side effects like hirsutism and many others. To overcome the side effects associated with steroid use in kidney transplantation, in particular cardiovascular adverse events, few protocols and suggestions of steroid free or low steroid regimens have been used.
The provided article reviewed studies on strategies for steroid minimization or avoidance:
(1) CS avoidance
(2) CS withdrawal:
1- Early withdrawal (usually 3-6 mo after Tx) OR
2- Late withdrawal (at least 6 mo after Tx).
(1) CS avoidance
Steroid avoidance strategies have been evaluated in few studies inclusing Basiliximab and antiyhmoglobulins as induction and CNI based maintenance in addition to MMF.
Basiliximab+EC-MPS+cyclosporins vs Basiliximab+EC-MPS+cyclosporins+ standard dose STEROIDS vs Basiliximab+EC-MPS+cyclosporins+ low dose STEROIDS, in low risk patients. Results showed significantly higher risk of rejection in the steroid avoidance group.
Another study evaluated induction with r-ALG followed by maintenance either tacrolimus/MMF/steroids vs tacrolimus/MMF. Results showed no difference in acute rejection and allograft with very early CS withdrawal at a follow-up time of 12 mo. However in the steroid free group, higher interstitial fibrosis rate was noted.
(2) CS withdrawal:
1- Early withdrawal (usually 3-6 mo after Tx): Results of the studies are heterogenous. . Pascual et al. reported that patient and graft survival are not affected by early CS withdrawal up to 3 years post transplant. Other study demonstrated higher acute rejection rate with early steroid withdrawal in patients treated with cyclosporine.
2- Late withdrawal (at least 6 mo after Tx). Results of this approach are not in favor of clinical use as it was associated with higher rate of rejection.
In RCT involving 212 patients, the incidence of biopsy proven acute rejection was found in 4% of CS withdrawal arm versus control arm. At 2 years follow up, patient and graft survival was not different between the 2 groups. No difference in allograft function. In CS withdrawal group no change in the metabolic profile.
How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
Inclusion criteria:
Uncontrolled DM
Uncontrolled hypertension
Obese patients
Osteoporosis
Very low risk recipients
Exclusion criteria
High risk patients
Corticosteroids(CS) are associated with many side effects ,so decrease of its use was thought about. Trials of avoidance or withdrawal had conflicting results in literature.
Maintenance therapy with low dose CS
either early CS withdrawal or low dose maintenance showed no difference in death rate, death censored graft los and moderate -severe rejection.
Avoidance of CS
Avoidance of CS needs induction with lymphocyte depleting agent to avoid risk of rejection.
Withdrawal of CS
Early withdrawal up to 3 years did not affect graft survival, with higher acute rejection in those treated with cyclosporine.
Late withdrawal of CS : BPAR was found in 4%and patient and graft survival not affected at 2 years of follow up. Also, allograft function was not affected.
2- CS minimization looks suitable in non sensitized ,young ,patients without ischemic heart and GN is not the primary disease. CS minimization should be avoided in case of DGF ,DCD and prolonged cold ischemia time
Uncontrolled DM& hypertension ,obesity ,osteoporosis ;generally low immunologic risk patients are situations that that regimen could be used and the reverse applies in case of high risk patients
CS continue to be key component of the therapeutic armamentarium in renal transplantation. A push toward the exclusion of CS from immunosuppressive regimens throughout the induction and maintenance phases has evolved in order to decrease the plethora of negative effects associated with continuous CS usage. When compared to CS continuation, CS reduction techniques have resulted in a higher incidence of acute rejection than when CS is avoided. These acute rejection episodes, on the other hand, are considered modest and treatable with medication. Furthermore, they do not seem to have a negative impact on patient mortality, allograft survival, or allograft function when patients are followed for up to five years.
In spite of this, the observed tendency toward greater fibrosis is concerning, and it calls for the development of randomized controlled trials with longer follow-up to ascertain the real repercussions of CS reduction. The use of CS minimization protocols has been associated with a reduction in adverse effects (particularly improvement in dyslipidemia), but these findings have not always been reproducible, and it is unclear whether they could translate into a reduction in cardiovascular events in the clinical setting.
Achieving CS reduction cannot be suggested to all kidney transplant patients at this time, because of the limitations of technology.
different protocol:
Low dosage CS: CS maintenance as compared to CS avoidance. Induction using T cell depleting drugs or IL-2R blockers is standard. Five years of follow-up There was no difference in patient mortality, death censored graft loss or moderate/severe rejection in low dosage CS, however, CAN be higher in patients who avoided CS.
Avoiding CS increased the risk of rejection compared to receiving low dosage CS, and the rate of rejection was higher among non-induction recipients. After 12 months, the CS avoidance arm had greater interstitial fibrosis.
The risk of AR is higher in cyclosporine-based regimens, however, patients and graft survival did not vary after 3 years.
Late CS withdrawal: The least favourable regime due to steroid complications and significant risk of AR. The incidence of AR is high with the regime, although graft survival did not change after 2 years.
Finally, low dosage CS is the ideal IS method, although it may be tailored to certain recipient populations.
I will avoid steroids in patients, including (0 mismatches, type 1 DM with a good HLA match.
Exclusion: high immunological risk(poor HLA match, pretransplant DSA).
Corticosteroids (CS) has been included in IS regimens since the start of transplantation, but their use is associated with many side effects due to their non specific mechanism of action, so that efforts was made to minimize the exposure to these medications.
Strategies for CS minimization are:
there is overlap between these categories found in the literature.
The efficacy of CS minimization depends on the intensity of other IS medications and the immunological risk of the patient.
Data from CS minimization studies produced conflicting results, some studies showed a reduction in CV risk factors such as dyslipidemia, while others are not. some studies showed increased risk of rejection but no effect on graft survival.
So, the aim of this study was to identify the optimal management strategy which provide maximum benefit for different patients subsets and improve transplant outcome.
Low dose CS as maintenance therapy:
In the RCT with follow up period of 5 years, 386 patients assigned to either early CS withdrawal at one week post transplant or CS continuation with maintenance dose of 5mg/day at 6 months, there were no difference in the rate of death, death-censored graft loss and moderate-severe rejection.
CS avoidance:
Attempts to use CS avoidance regimens in the absence of induction IS resulted in a high rate of rejection. induction with lymphocyte depleting agents seems to be the optimal option for CS avoidance regimen without putting the patient at risk of rejection.
CS withdrawal
Early withdrawal:
In a systematic review involve 9 studies, 1820 patients the findings are:
Late CS withdrawal:
Represent the least favorable method of CS minimization.
In RCT involving 212 patients:
Based on this evidence, patients who are suitable for CS minimization therapy are:
contraindication to CS minimization:
CS is commonly used in IS regime, but it had several serious side effects as CV complications( TH, DM, & dyslipidemia) & non CV side effects ( growth retardation, poor worn healing, & bone complications). Due to wide range of CS side effects its tried to minimizing the exposure to it in recipients with stable renal function. CS minimization can be classified into:
Several trials study the CS minimization regimes benefit & harm but the result had heterogeneity. Some of these trial show reduce in CV risk factors( hyperlipidemia) without proven benefit in reducing CV disease purden.
Aim of this study is to find an appropriate treatment strategy that maximizing benefits in different patients subsets with out increase risk of graft loss.
Low dose CS: using low CS as maintenance were studies in comparison to CS avoidance. All recipients receive induction with T cell depleting agents or IL-2R blocker. The patients followed for 5 years. The result show that there was no difference in patients death, death censored graft loss & moderate/ severe rejection in low dose CS, but it was found that CAN was more among patients with CS avoidance regime.
CS avoidance: It shown that risk of rejection increased in patients with CS avoidance regime when compared with patients receive low dose CS, & the incidence of rejection was more among recipients not receive induction. Graft survival not different 12 months of follow-up but interstitial fibrosis was more in CS avoidance arm.
Early CS withdrawal: It was found that the risk of AR is more in cyclosporine based regime but patients & graft survival didn’t differ after 3 years of follow-up.
Late CS withdrawal: Its the least favorable regime because steroid complication established by this period & the risk of AR was high in this period. It was found that incidence of AR is high with regime but graft survival didn’t differ during 2 years follow-up.
In conclusion low dose CS is the best IS strategy, but CS minimized regime can be offered for special recipients subgroups.
In my center I prefer to use low dose CS, but can use CS avoidance regime in some patients :
Inclusion criteria : first transplantation , no history of sensitization, young, severe osteoporosis
Exclusion criteria : high immunological risk, elderly , GN as primary disease
Please summarise this article.
Although corticosteroids are corner store in induction and maintenance immuuno suppression protocols ,their side effects negatively impact patient compliance .these side effect include hypertension ,diabetes , dyslipidaemia , growth retardation impaired wound healing ,cataract , bone problem and cosmetic effects .minimizing the exposure to corticosteroids in transplant recipients with stable allograft has been manifested by renal transplant clinicians to reduce their associated side effects .
The strategies for corticosteroids minimization are;
1-coricosteroids withdrawal following a period after transplantation
-very early withdrawal (less than 2 weeks ) has been classified under both CS avoidance and withdrawal .
-early withdrawal ;usually 3-6 months after transplantation .
-late withdrawal ; at least 6 months after transplantation .
2- corticosteroids avoidance
3- low dose corticosteroids maintenance therapy
Safe application of CS minimization required ;
-induction immunosuppression
-calcinurin maintenance therapy
-patient at low immunological risk are considered as ideal candidate for the implementation for CS minimization .
Low CS dose as maintenance therapy ;
acute rejection rates are constantly lower when CS maintenance regimens are used. Patient and allograft survival seems not to be influenced by CS minimization, but it is unknown if this remains the same with longer
follow-up. chronic allograft nephropathy (CAN) incidence at 5 years was more than double with very early CS withdrawal compared to a continuation. Although CS minimization may permit some improvement in cardiovascular risk factors, data are not consistent about it. As far as it concerns non cardiovascular adverse events, very early CS withdrawal reduced bone fractures and a vascular necrosis but it was paradoxically associated with more frequent sub capsular cataract.
CS avoidance ;
induction with lymphocyte depleting agents seems to be the optimal option for consolidating the benefits of CS avoidance strategies without putting renal allograft at risk of acute rejection. A beneficial effect of very early CS withdrawal was shown for new onset diabetes mellitus, sub capsular cataract, and a vascular necrosis.
Studies found no difference in patient and allograft survival, acute rejection, incidence of CAN and allograft function between the two arms at 3 years. A lower frequency of new-onset diabetes mellitus was noted in the very early CS withdrawal group.
Early CS withdrawal ;
It is unknown if induction with lymphocyte depleting agents or antiinterleukin-2 receptor monoclonal antibodies were used in any of the studies, it would have any meaningful impact on the results. Overall, evidence about the benefit risk ratio of early CS withdrawal is weaker than that of CS avoidance and follow-up times are shorter.
Although reduction of total cholesterol levels was observed with early CS withdrawal, no significant difference was found for any of the other cardiovascular or non-cardiovascular adverse events.
Late CS withdrawal ;
It is apparent that certain CS-related complications would already have been established by that time. it is well known that a rapid deterioration in osteoporosis occurs within the first post transplant year. Moreover, acute rejection risk is clearly increased upon late withdrawal of immune suppressants as dictated by cases of non-compliant patients.
CS withdrawal resulted in reduced mean blood pressure but had no effect on other metabolic risk factors. The reduction was also noted in the incidence of cardiovascular parameters. patient and allograft survival was better in late CS withdrawal .
In conclusion;
Although corticosteroids have been traditional components of immunosuppressive regimens in renal transplantation, corticosteroid minimization strategies are developed in an attempt to mitigate their many side effects.
The benefit from this approach must be balanced against the risk of acute rejection due to insufficient immune suppression and the potential harm to allograft survival.
Patient selection according to the immunological risk and the induction immunosuppression is the principal factors that determine the success of corticosteroid withdrawal and avoidance protocols.
How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
Inclusion criteria ;
Low immunological risk patient with or at risk of the following;
-Obesity
-Osteoporosis
-Diabetes , hypertension , dyslipidaemia
-Cardiovascular disease
-Cosmotic side effects of steroids.
Exclusion criteria
High immunological risk
Absence of metabolic indication
inclusion criteria ;
low immunological risk
young patient
exclusion criteria
high immunological risk
patient at risk of recurrence GN
1. Please summarise this article.
Corticosteroid minimization strategies are established to avoid steroids sideeffects. A balance must be made between the risk of acute rejection and their side effects.
Methodolgy
The corticosteroids minimization strategies are either avoidance ( very early withdrawal )or withdrawal after a period of transplantation which could be either early (3-6 months post transplantation )or late withdrawal ( after 6 months from transplantation)
Low immunological risk cases are more suitable to apply this regimen
Induction immunosuppression is needed and maintenance therapy involving calcineurin inhibitors is the safe protocol to apply this regimen .
The aim of this study is to reach the best management protocol, without compromising safety and improving Tx net results.
RESULTS
–Low CS dose as maintenance therapy
In a RCT they compared 2 groups one with corticosteroid withdrawal 1 week post transplantation and the other tappering it to 5 mg at 6 months.
Induction immunosuppression with ATG or basiliximab and maintenance with tacrolimus and MMF were given.
After 5 y follow up period there was no difference in patient survival ,acute rejection and GFR but biopsy-confirmed acute rejection was less in the CS continuation group and in ATG induction group but was not statically significant in the latter .
Chronic allograft nephropathy was higher in early withdrawal group
Follow up for longer times till 10 y is needed to justify the results
–CS avoidance
A multicenter RCT used basiliximab for induction and maintenance with cyclosporine and MMF compared no CS to CS withdrawal by day 7 to standard CS.
BPAR was higher with CS avoidance and withdrawal groups and no difference was noted regarding e GFR , patient and allograft survival.
Multiple other studies used other induction and maintenance choices and concluded the same previous results
Meanwhile induction with lymphocyte depleting agents as lately used alemtuzumab seems the best choice for preserving CS avoidance strategies privileges without risking the allograft.
–CS withdrawal
· Early CS withdrawal:
Cyclosporine use as maintenance wasnot possible but Tac and MMF usage enabled reapplying this strategy.
Multiple studies demonstrated that patient and allograft survival till 3 years after Tx is not affected by early Cs withdrawal ,but induction therapy wasnot used in those studies
· Late CS withdrawal:
Is less prefered strategy as after 6 months already CS side effects had occurred and graft is liable for late rejection.
A study concluded that patient and allograft survival was better than retrospectively matched controls over a follow up time of 7 years with no difference in acute rejection rates for patients with CS withdrawal more than 6 mo from Tx
Discussion
The favorable effects of CNS minimization protocol in low immunological risk cases encouraged using it with high risk cases as well.
This strategy was of special interest particularly in pediatric group to avoid side effects involving growth retardation,etc
On the other hand this protocol disadvantage is the high rate of post transplant GN recurrence .
This protocol is not suitable for elderly although they have lower rate of acute rejection but it is more severe if occurred.
2-How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
-Inclusion criteria
Low imunological risk as first transplant ,
<20% PRA,
unsensitized to HLA antigens,
low risk of GN recurrence
Young patients
-Exclusion criteria
High immunological risk as multiple transplant , multiparus ,
blood transfusion
highly sensitized cases
Elderly population
Transplant recipients with delayed graft function (DGF) and prolonged cold ischemia time and patient receiving a graft from a donor post cardiac arrest
Steroid minimization protocol
Aim to decrease the incidence of complications like cardiovascular comorbidities , HTN, DM, bone disease like osteoporosis, also cosmetic disfigurement will leads to non compliance to medications and psychological issues which in turn predispose to acute rejection or CAN.
Benefits against risks of under immunosuppression should be considered, because of the risk of steroid sensitive acute rejection, which will affect graft outcome.
Steroid minimization can be divided into :
1- Steroid avoidance or very early withdrawal less than 2 weeks post-transplant
2- Steroid withdrawal which can be very early less than 2 weeks post-transplant, early less than 6 months post-transplant or late after 6 months post-transplant.
The ideal candidate for CS minimization protocol is immunological low risk patients who are non-sensitized, and should be first transplant, and their original disease should be non-GN. Also induction should be given and CNI should be included in the protocol.
Early withdrawal should be done to get maximum benefits from avoidance or withdrawal of steroid
CS still an important agent of the immunosuppression protocol in renal transplantation.
CS elimination from induction and maintenance immunosuppression regimens has developed to reduce its side effects associated with chronic CS use.
CS minimization strategies have resulted in an increased incidence of acute rejection compared to CS continuation.
steroid minimization protocol in my practice is not well defined except when there is dramatic complications
Corticosteroids are considered the cornerstone of immune suppression in renal transplantation. It is used in induction protocols, an important member of triple maintenance immunosuppressive therapy recommended for most renal transplant patients and it is considered to be a key component in the treatment of rejection.
Side effects of glucocorticoids
Because of the side effects of corticosteroids, there are many trials on corticosteroid minimization which include one of the following protocols:
1. Complete withdrawal which can be done either early within 3- 6 months after transplantation or late after 1 year.
2. Complete avoidance from the start
Possible drawbacks in the use of corticosteroid minimization protocols
Glucocorticoid minimization should not be initiated in the following patients (exclusion criteria):
Precautions in the use of CS minimization protocol (inclusion criteria):
Please summarise this article.
Side effects of corticosteroid are –
hypertension
diabetes mellitus
dyslipidemia
growth retardation
impaired wound healing
subcapsular cataract
bone problems (osteoporosis, fractures, avascular necrosis)
cosmetic effects
Strategies for CS minimization can be categorized as:
(1) CS avoidance;
(2) CS withdrawal following a period after Tx. further divided as early withdrawal (weeks or months after Tx, usually 3-6 mo after Tx) or late withdrawal (at least 6 mo after Tx).
CS avoidance-
In the Astellas Corticosteroid Withdrawal Study), Woodle et al assigned 386 renal transplant recipients with PRA (panel reactive <25%) to very early CS withdrawal at 1 week post-transplant or CS continuation tapered to 5 mg prednisolone per day at 6 month.
induction immunosuppression-
68% of them with the lymphocyte-depleting agent anti-thymocyte
globulin (ATG)
32% with anti-interleukin-2 receptor monoclonal antibodies.
Maintenance immunosuppressive-
tacrolimus and mycophenolate mofetil (MMF).
After a follow-up of 5 years-
no difference was found in
the rate of patient death
death-censored allograft loss
moderate/severe acute rejection.
biopsy-proven acute rejection rates were numerically lower with ATG induction than
with anti-interleukin-2 receptor monoclonal antibodies in very early CS withdrawal patients.
Serum creatinine and creatinine clearance were similar between the two arms at 5 years.
chronic allograft nephropathy (CAN) incidence at 5 years was more than double in the early CS withdrawal arm.
Early CS withdrawal-
Patient and allograft survival is not affected by early Cs withdrawal up to 3 years after Tx. Total acute rejection rates were higher with early CS withdrawal in cyclosporine-treated patients. no significant difference was found for any of the other cardiovascular or non-cardiovascular adverse events. It is worth mentioning that induction immunosuppression was not used in any of the studies.
Late CS withdrawal:
It appears that late CS withdrawal (more than 6 mo and possibly years after Tx) represents
the least favorable method of the CS minimization strategies.
In contrast to the perceived benefits of CS minimization in younger transplant recipients, this strategy may not be suitable for elderly patients.
CS minimization may not also be suitable for transplant recipients with delayed graft function
(DGF) and prolonged cold ischemia time.
How would you apply this immunosuppression strategy in your centre (set inclusion and exclusion criteria)?
INCLUSION –
Paediatric patient non sensitised.