Randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 6 months

Transplantation. 2003 Apr 27;75(8):1213-20. doi: 10.1097/01.TP.0000062837.99400.60.


Background: This is the first report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. Results at 6 months of follow-up are presented.

Methods: Before transplantation, patients were randomized to receive tacrolimus plus corticosteroids with sirolimus (n=185) or MMF (n=176). The primary endpoint of the study was the incidence of biopsy-confirmed acute rejection. Patient and graft survival, renal function, and composite endpoints also were evaluated. Safety was assessed by monitoring laboratory parameters and adverse events.

Results: By 6 months of follow-up, the incidence of biopsy-confirmed acute rejection was similar in both treatment groups (13.0% tacrolimus+sirolimus vs. 11.4% tacrolimus+MMF; P=0.64 log-rank). Patient survival (97.3% tacrolimus+sirolimus vs. 97.7% tacrolimus+MMF) and graft survival (93.0% tacrolimus+sirolimus vs. 95.5% tacrolimus+MMF) were equivalent (P=0.53, overall survival log-rank). There was a significantly higher incidence of study drug discontinuation in patients receiving sirolimus (21.1% vs. 10.8%; P=0.008). Renal function was significantly better in the MMF-treatment group (serum creatinine 1.44+/-0.45 mg/dL vs. 1.77+/-1.42 mg/dL; P=0.018). Hyperlipidemia was significantly more prevalent in the sirolimus-treatment group. Diastolic blood pressure was significantly higher in sirolimus-treated patients. There were significantly more leukopenia and gastrointestinal adverse events in the MMF-treatment group. The incidence of posttransplant diabetes mellitus was 7.6% in the sirolimus group and 7.7% in the MMF group.

Conclusion: Tacrolimus is equally effective in renal transplantation when combined with sirolimus or MMF. The tacrolimus-MMF combination may be superior in terms of improved renal function and improved cardiovascular risk factors including hyperlipidemia and hypertension.

Publication types

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

MeSH terms

  • Acute Disease
  • Adult
  • Cardiovascular Diseases / etiology
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Graft Rejection / epidemiology
  • Graft Survival
  • Humans
  • Hyperlipidemias / epidemiology
  • Hypertension / epidemiology
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Kidney / physiopathology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use*
  • Risk Factors
  • Sirolimus / adverse effects
  • Sirolimus / therapeutic use*
  • Survival Analysis
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Time Factors


  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus