Results of a Prospective Randomized Trial of Sirolimus Conversion in Kidney Transplant Recipients on Early Corticosteroid Withdrawal

Background. The use of calcineurin inhibitors is associated with chronic nephrotoxicity and lower glomerular filtration rate (GFR). As a result, one strategy of transplant immunosuppression is calcineurin inhibitor elimination. Methods. The aim of this study was to determine the outcome of a prospective randomized trial of kidney transplant recipients receiving rapid corticosteroid withdrawal, tacrolimus and mycophenolate mofetil (MMF) for 1 month followed by randomization to switch to sirolimus-MMF or to stay on tacrolimus-MMF. The primary outcome was the difference in measured GFR at 1 year using intention-to-treat analysis. Results. Sixty patients were randomized to stay on tacrolimus-MMF and 62 to sirolimus-MMF. Actual graft survival (including death) at 2 years was 98.4% in the sirolimus group, 96.7% in the tacrolimus group. Sixty-three percentage of the patients in the sirolimus group withdrew during the 2-year period of the study compared with 18% of the tacrolimus group (P < 0.0001), primarily related to rejection or medication side effects. Rejection during the first year occurred in 5% of the tacrolimus group and 13% of the sirolimus group (P = 0.15). Measured GFR at 1 year (mean +/- SD) was 57.4 +/- 20.7 mL/min/1.73 m(2) in the sirolimus group and 62.7 +/- 26.5 mL/min/1.73 m(2) in the tacrolimus group (95% CI of difference -3.7-14.4). Conclusions. We conclude that conversion from tacrolimus-MMF to sirolimus-MMF at 1 month posttransplant in kidney recipients on rapid steroid withdrawal is poorly tolerated and does not improve GFR at 1 year.