A Randomized, Open-Label Study of Sirolimus Versus Cyclosporine in Primary De Novo Renal Allograft Recipients

作者：Flechner Stuart M^*; Gurkan Alihan; Hartmann Anders; Legendre Christophe M; Russ Graeme R; Campistol Josep M; Schena Francesco P; Hahn Carolyn M; Li Huihua; Korth Bradley Joan M; Tai Sandi See; Schulman Seth L

来源：Transplantation, 2013, 95(10): 1233-1241.

DOI：10.1097/TP.0b013e318291a269

• Acute allograft rejection
• Delayed graft function
• Sirolimus
• Cyclosporine
• Mycophenolate mofetil

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. %26lt;br%26gt;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. %26lt;br%26gt;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%26lt;0.001); and higher rates of discontinuations due to adverse events (17.4% vs. 6.8%; P=0.001). %26lt;br%26gt;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.

• 出版日期2013-5-27