title: A randomized, open-label study of sirolimus versus cyclosporine in primary de novo renal allograft recipients.
abstract: 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. 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA. flechns@ccf.org
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Flechner
authors.forename: Alihan
authors.initials: A
authors.lastname: Gurkan
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.forename: Christophe M
authors.initials: CM
authors.lastname: Legendre
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Russ
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Schena
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hahn
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.forename: Joan M
authors.initials: JM
authors.lastname: Korth-Bradley
authors.forename: Sandi See
authors.initials: SS
authors.lastname: Tai
authors.forename: Seth L
authors.initials: SL
authors.lastname: Schulman
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use*; D051799:Delayed Graft Function / Q000209:etiology; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D020123:Sirolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus