A randomized, open-label study of sirolimus versus cyclosporine in primary de novo renal allograft recipients.

Background. Despite a decreased incidence of acute rejection and early renal allograft loss due to calcineurin inhibitors (CNIs) in transplant recipients, nephrotoxicity associated with long-term CNI use remains an important issue. This study evaluated whether a CNI-free regimen, including sirolimus, mycophenolate mofetil, corticosteroids, and anti-interleukin-2 receptor antibody induction, results in improved long-term renal function. Methods. This open-label, randomized, parallel group, comparative study in primary de novo renal transplant recipients was planned for 48 months but terminated early because of high acute rejection rates in the sirolimus arm. Results. Enrollment was stopped after,12 months, with 475 transplanted patients randomized (2:1) to sirolimus (n=314) or cyclosporine A (CsA) treatment (n=161). Mean length of follow-up after transplantation was 190 days; this article focuses on available data through 6 months. MeanTSD on-therapy Nankivell-calculated glomerular filtration rate was not significantly different between the sirolimus (69.1 +/- 18.7 mL/min) and CsA (66.0 +/- 15.2 mL/min) treatment groups. Occurrence and length of delayed graft function was not significantly different between groups. Patients in the sirolimus group experienced numerically lower survival rates (96.9% vs. 99.4%; P=0.14), with nine deaths reported with sirolimus and one with CsA; higher rates of biopsy-confirmed acute rejection (21.4% vs. 6.1%; P<0.001); and higher rates of discontinuations due to adverse events (17.4% vs. 6.8%; P=0.001). Conclusion. A sirolimus-based, CNI-free immunosuppressive regimen, when used with mycophenolate mofetil, corticosteroids, and antiYinterleukin-2 receptor antibody induction, was associated with high rates of biopsy-confirmed acute rejection compared with CsA-based immunosuppression and is not recommended.