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 in the sirolimus group and 62.7±26.5 mL/min/1.73 m 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.