A Meta-analysis of Immunosuppression Withdrawal Trials in Renal Transplantation

Since the publication of previous meta-analyses of cyclosporine (CsA) and prednisone withdrawal in renal transplant recipients, several additional randomized controlled trials with longer follow-up have been reported. Currently, in nine prednisone withdrawal trials (n = 1461), the proportion of patients with acute rejection was increased by 0.14 (95% confidence interval = 0.10 to 0. 17, P < 0.001). In nine prednisone withdrawal trials (n = 1899), the relative risk (RR; RR = 1.0 indicates no risk) of graft failure after withdrawal was also increased (RR = 1.40; range, 1.09 to 1.70, P = 0.012). There was no evidence of between-study heterogeneity for either acute rejection or graft failure in the prednisone withdrawal trials by a chi(2) test (P > 0.05). In 10 CsA withdrawal trials (n = 1049), the proportion of patients with acute rejection was increased by 0.11 (0.07 to 0.15, P < 0.001). In 12 trials (n = 1151), the RR of graft failure after CsA withdrawal was 1.06 (95% confidence interval, 0.82 to 1.29, P = 0.646), but a chi(2) test indicated that there was study heterogeneity. However, there was no evidence of heterogeneity in the six studies (n = 632) with at least 4.0 yr (5.8 +/- 1.7) of follow-up (RR = 0.92; range, 0.64 to 1.20, P = 0.569) or in the seven trials (n = 962) published in peer-reviewed journals (RR = 0.95; range, 0.70 to 1.20 P = 0.682). Finally, in three trials (n = 259) that compared CsA and prednisone withdrawal, there was a nonsignificant trend for less graft failure with CsA withdrawal (RR = 0.63; range, 0.08 to 1.16, P = 0.190). Thus, unlike prednisone withdrawal, CsA withdrawal in select patients seems to impart little risk of long-term graft failure.