Steroid withdrawal in renal transplant patients on triple therapy with a calcineurin inhibitor and mycophenolate mofetil:: A meta-analysis of randomized, controlled trials

Background. Two previous meta-analyses of randomized, controlled trials of steroid withdrawal after renal transplantation have shown significant increases in acute rejection (both analyses) and graft failure rates (the last analysis). A new examination of this topic including only randomized, controlled trials based on currently used, new, potent therapy with calcineurin inhibitors and mycophenolate mofetil (MMF), avoiding early trials with azathioprine, is justified. Methods. Steroid withdrawal in patients on triple therapy including a calcineurin inhibitor and MMF was assessed through meta-analysis of randomized, controlled trials in which intention-to-treat rates of acute rejection and renal allograft failure were established after steroid withdrawal or continuation. Results. Six trials were included, four in patients receiving cyclosporine and two in patients receiving tacrolimus. The risk ratio (RR) for acute rejection was 2.28 (95% confidence interval [CI], 1.65-3.16; P<0.00001) and the pooled risk difference (RD) was 0.08 (95% CI, 0.05-0.11; P<0.001), indicating that the proportion of patients with acute rejection after prednisone withdrawal was significantly higher compared with controls. The RR for graft failure was 0.73 (95% CI, 0.42-1.28; P=0.27) and the RD was -0.01 (95% CI, -0.03-0.01; P=0.28), indicating that the proportion of patients with graft failure after withdrawal was not significantly different from that observed in controls. Total cholesterol was significantly lower after steroid withdrawal (weighted mean difference, -0.53 muM (95% CI, -0.70 to -0.36; P<0.0001). Conclusions. Renal allograft recipients on triple therapy with a calcineurin inhibitor, MMF, and steroids are at low but significant risk of acute rejection after steroid withdrawal but do not suffer an increased risk of early graft failure. It is necessary to extend controlled follow-up to confirm graft function stabilization.