Conversion from calcineurin inhibitors to sirolimus for chronic renal allograft dysfunction: a systematic review of the evidence

Transplantation. 2006 Nov 15;82(9):1153-62. doi: 10.1097/


Background: Conversion from a calcineurin inhibitor to sirolimus has been used as a strategy to improve deteriorating renal allograft function but the efficacy and safety of this intervention is unknown.

Methods: We performed a systematic review of studies that involved conversion from a calcineurin inhibitor to sirolimus in kidney transplantation. The search yielded five randomized trials (n=1,040 patients) and 25 nonrandomized studies (n=977 patients).

Results: In the randomized trials, conversion to sirolimus improved short-term creatinine clearance (weighted mean difference 6.4 mL/min; 95% CI 1.9 to 11.0) compared to controls. In the nonrandomized studies, renal function improved or stabilized in 66% (95% CI 61% to 72%), creatinine clearance improved (weighted mean change 5.7 mL/min; 95% CI 1.4 to 10.1), cholesterol increased (weighted mean change 20.8 mg/dL; 95% CI 11.2 to 30.4) and triglycerides increased (weighted mean change 40.1 mg/dL; 95% CI 18.6 to 61.7). Sirolimus was discontinued by 28% of patients (95% CI 0 to 59%) in the randomized trials and 17% (95% CI 12 to 22%) in the nonrandomized trials.

Conclusion: Conversion to sirolimus is associated with an improvement in short-term renal function. However, given the discontinuation rate and potential side effects, adequately powered randomized trials with longer follow-up of hard outcomes are needed to determine whether this strategy leads to a lasting benefit in the clinical care of transplant recipients.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Calcineurin Inhibitors
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Failure, Chronic / prevention & control*
  • Kidney Transplantation*
  • Randomized Controlled Trials as Topic*
  • Sirolimus / adverse effects
  • Sirolimus / therapeutic use*


  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Sirolimus