Abstract
BackgroundImmunosuppressive regimens in renal transplantation frequently contain corticosteroids, but many centers withdraw steroids as a consequence of unwanted side effects of steroids. The optimal timing to withdraw steroids after transplantation, however, remains unclear. The aim of this study was to determine an optimal time point following kidney transplantation that is associated with reduced mortality without jeopardizing the allograft to allow safe discontinuation of steroids.MethodsWe conducted a retrospective cohort study and computed a concatenated landmark-stratified Cox supermodel to estimate hazard ratios and 95% confidence intervals for mortality and graft loss using dynamic propensity score matching to adjust for confounding by indication.ResultsA total of 6070 first kidney transplant recipients in the Austrian Dialysis and Transplant Registry who were transplanted between 1990 and 2012 were evaluated and classified according to steroid treatment status throughout follow-up after kidney transplantation; 2142 patients were withdrawn from steroids during the study period. Overall, 1131 patients lost their graft and 821 patients in the study cohort died. Steroid withdrawal within 18 months after transplantation was associated with an increased rate of graft loss compared to steroid maintenance during that time (6 months after transplantation: HR = 1.8; 95% CI, 1.3 to 2.6; 18 months after transplantation: HR = 1.3; 95% CI, 1.1 to 1.6; 24 months after transplantation: HR = 1.2; 95% CI, 0.9 to 1.5), while mortality was not different between groups.ConclusionsOur findings suggest that steroid withdrawal after anti-IL-2 induction in the first 18 months after transplantation is associated with an increased risk of allograft loss.
Highlights
Immunosuppressive regimens in renal transplantation frequently contain corticosteroids, but many centers withdraw steroids as a consequence of unwanted side effects of steroids
While earlier meta-analyses of these trials reported an increased rate of acute rejections and graft loss after steroid withdrawal compared with steroid maintenance, more recent meta-analyses included trials conducted with newer immunosuppressants and found no difference in graft loss [10, 22,23,24]
Our results demonstrate that steroid withdrawal within the first 18 months after transplantation is associated with an increased rate of graft loss compared to steroid maintenance during that time, while mortality is unaffected by steroid withdrawal at any time point after transplantation compared to steroid maintenance
Summary
Immunosuppressive regimens in renal transplantation frequently contain corticosteroids, but many centers withdraw steroids as a consequence of unwanted side effects of steroids. The aim of this study was to determine an optimal time point following kidney transplantation that is associated with reduced mortality without jeopardizing the allograft to allow safe discontinuation of steroids. The increased risk of acute rejection persisted, subgroup analyses indicated that contemporary immunosuppression reduced the risk of acute rejection, and steroid withdrawal 3–6 months following kidney transplantation was suggested. Current clinical practice guidelines discourage steroid withdrawal beyond the first week after engraftment [25] In view of this inconsistency of recommendations, steroid withdrawal is managed differently in clinical practice and there is no consensus on the optimal timing for steroid withdrawal after kidney transplantation. Long-term outcomes after steroid withdrawal remain uncertain to date due to the limited follow-up in rather small randomized trials [11]
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