A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation: three-year analysis

Transplantation. 2006 Mar 27;81(6):845-52. doi: 10.1097/01.tp.0000203894.53714.27.


Background: We report three-year (interim) effects of combining sirolimus (Siro) vs. mycophenolate mofetil (MMF) as adjunctive therapy with calcineurin inhibitors (CI) in renal transplantation in the three different CI-based regimens.

Methods: Between May 2000 and December 2001, 150 recipients of deceased donor (DD) and living donor (LD) kidney transplants were randomized into three groups (n=50/group): Group A (Tacro/Siro), Group B (Tacro/MMF) and Group C (CsA/Siro). This report details drug dosing and monitoring, protocol discontinuance, biopsy-proven rejection, graft failure, other adverse events, and death at 36 months postoperatively.

Results: Actual patient and graft survival respectively in Group A was 90% and 82%, in Group B was 92% and 88%, and in Group C was 96% and 88% (not significant). Biopsy-confirmed acute rejection incidents showed a trend in favor of Group B (10%) vs. Group A (26%) and Group C (20%) combined (P=0.07). The geometric mean */SE serum creatinine concentration and arithmetic mean +/- SE Cockroft-Gault creatinine clearance calculations, respectively, were 1.39*/1.1 and 72.8+/-4.3 for Group A, 1.36*/1.1 and 72.1+/-4.1 for Group B, and 1.60*/1.1 and 61.8+/-3.8 for Group C, a statistically favorable difference for Group B over Group C (P=0.04). There was also less de novo development of posttransplant diabetes mellitus and lipid disorders in Group B vs. A and C (P<0.04).

Conclusions: This three-year (interim) analysis has indicated a trend towards better graft function, fewer endocrine disorders, and fewer acute rejection episodes comparing adjunctive MMF and Tacro vs. Siro and Tacro or Siro and CsA, in the dosages used.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Pressure
  • Cross-Over Studies
  • Diabetes Mellitus / etiology
  • Dyslipidemias / etiology
  • Female
  • Graft Rejection / epidemiology
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Incidence
  • Kidney / physiopathology
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / mortality
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / blood
  • Sirolimus / administration & dosage*
  • Sirolimus / blood
  • Tacrolimus / administration & dosage*
  • Tacrolimus / blood


  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus