Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation

Transplantation. 2004 Apr 27;77(8):1228-35. doi: 10.1097/


Introduction: This study examines the efficacy and toxicity of sirolimus used as primary immunosuppression in combination with reduced dose tacrolimus (calcineurin inhibitor [CI]-sparing regimen) or mycophenolate mofetil (CI-free regimen) in high-risk cadaveric renal transplantation.

Methods: Seventy subjects were treated in a quadruple sequential protocol in which 41 were treated with a CI-sparing regimen and 29 were treated with a CI-free regimen. The efficacy and toxicity profiles of these regimens were prospectively monitored and compared.

Results: The study consisted of African Americans (71%), cadaveric donors (100%), donors aged more than 50 years (30%), and patients with delayed graft function (47%). At 1 year, patient survival, graft survival, and incidence of biopsy-proven acute rejection were 98%, 80%, and 10%, respectively, in the CI-sparing group and 100%, 89%, and 7%, respectively, in the CI-free group. Three-month protocol biopsies were performed in 41% (17/41) and 67% (20/29) of the subjects in the CI-sparing and CI-free groups, respectively. Subclinical rejection was detected in 6% (1/17) and 15% (3/20) of the subjects in the CI-sparing and CI-free groups, respectively. Histologic evidence of chronic allograft nephropathy was more prevalent in the CI-sparing group. At 1 year, the mean estimated creatinine clearance was higher in the CI-free group than in the CI-sparing group (72.4 +/-20.0 mL/min vs. 50.5 +/-20.8 mL/min, P <0.01). The two regimens had similar toxicity profiles (hospital readmission, infection, wound complications, and metabolic complications).

Conclusions: Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk. The CI-free regimen is associated with better renal function at 1 year post-transplant. Long-term follow-up will aid in determining the risk and benefit ratio of these regimens.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cadaver
  • Calcineurin Inhibitors*
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology
  • Kidney Transplantation / physiology
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Prospective Studies
  • Safety
  • Sirolimus / administration & dosage*
  • Sirolimus / adverse effects
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects


  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus