title: Calcineurin inhibitor withdrawal from sirolimus-based therapy in kidney transplantation: a systematic review of randomized trials.
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.
authors.affiliation: Division of Nephrology, Kidney Research Center, Ottawa Health Research Institute, Ottawa, Ontario, Canada.
authors.forename: Atul V
authors.initials: AV
authors.lastname: Mulay
authors.forename: Naser
authors.initials: N
authors.lastname: Hussain
authors.forename: Dean
authors.initials: D
authors.lastname: Fergusson
authors.forename: Greg A
authors.initials: GA
authors.lastname: Knoll
mesh_terms: D000208:Acute Disease; D065095:Calcineurin Inhibitors; D004334:Drug Administration Schedule; D006084:Graft Rejection / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus