Steroid withdrawal in renal transplantation

Abstract

Over the last decade, steroid minimization became one of the major goals in pediatric renal transplantation. Different protocols have been used by individual centers and multicenter study groups, including early and late steroid withdrawal or even complete avoidance. The timing of steroid withdrawal determines if antibodies are used, as avoidance and early withdrawal require antibody induction, while late withdrawal typically does not. A monoclonal antibody was used in most protocols during an early steroid withdrawal together with tacrolimus and mycophenolate mofetil in low immunological risk patients. Polyclonal induction was reported as effective in high-risk patients. Cyclosporine A and mycophenolate mofetil were used in late steroid withdrawal with no induction. All described protocols were effective in terms of preventing acute rejection and preserving renal graft function. There was no superiority of any specific protocol in terms of clinical benefits of steroid withdrawal. Pre-puberty determined growth benefit while other clinical advantages, including better control of glycemia, lipids, and blood pressure, were age independent. It is not clear whether the steroid withdrawal increases the risk of recurrence of primary glomerular diseases post-transplant, however it cannot be excluded. There is no evidence to date for a higher risk of anti-HLA production in steroid-free children after renal transplantation. Key summary points--Current strategies to minimize the steroid-related adverse effects in pediatric renal graft recipients include steroid withdrawal, early or late after transplantation, or complete steroid avoidance--Early steroid withdrawal or avoidance is generally used following the induction therapy with mono- or polyclonal antibodies, while in late steroid withdrawal induction therapy was generally not used- Elimination of steroids (early or late) does not increase the risk of acute rejection and does not deteriorate long-term renal graft function- Early steroid withdrawal is possible in patients at high immunological risk using a combination of polyclonal antibody induction, tacrolimus, and mycophenolate mofetil- All protocols of steroid minimization showed relevant clinical benefits, however the growth-related benefit was limited to pre-pubertal patients in all but one of the studies- Adverse events of steroid withdrawal occurred in a higher incidence of post-transplant bone marrow suppression Key research points - There is no clear evidence of the impact of steroid withdrawal on the risk of recurrence of primary glomerulonephritis after renal transplantation in children, therefore further evaluation of this important issue should be performed in prospective trials- There is limited pediatric data on the risk of anti-HLA/donor-specific antibody production in steroid-free patients after renal transplantation. It is not clear whether the selection of the type of induction antibody (lymphocyte depleting versus short, two-dose administration of anti-IL2R inhibitor) is important in this term. The production of anti-HLA antibodies should then be monitored on a regular basis and analyzed in prospective trials.