Flechner, S.Gurkan, A.Hartmann, A.Legendre, C.Russ, G.Campistol, J.Schena, F.Hahn, C.Li, H.Korth-Bradley, J.Tai, S.Schulman, S.2015-01-072015-01-072013Transplantation, 2013; 95(10):1233-12410041-13371534-6080http://hdl.handle.net/2440/88561Background: 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. Mean±SD 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 anti–interleukin-2 receptor antibody induction, was associated with high rates of biopsy-confirmed acute rejection compared with CsA-based immunosuppression and is not recommended.en© 2013 Lippincott Williams & Wilkins, Inc.Acute allograft rejectionDelayed graft functionSirolimusCyclosporineMycophenolate mofetilJournal article002013853310.1097/TP.0b013e318291a2690003193360000112-s2.0-8487856953314286