Calcineurin inhibitor withdrawal from sirolimus-based therapy in kidney transplantation: a systematic review of randomized trials

Am J Transplant. 2005 Jul;5(7):1748-56. doi: 10.1111/j.1600-6143.2005.00931.x.

Abstract

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Acute Disease
  • Calcineurin Inhibitors*
  • Drug Administration Schedule
  • Graft Rejection / etiology
  • Humans
  • Hypertension / physiopathology
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / physiopathology
  • Kidney Transplantation*
  • Randomized Controlled Trials as Topic
  • Risk
  • Sirolimus / therapeutic use*

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Sirolimus