Effectiveness and safety of calcineurin inhibitor withdrawal in kidney transplantation: a meta-analysis of randomized controlled trials.

Background: The purpose was to compare the effectiveness and safety of calcineurin inhibitors (CNIs) withdrawal and continued therapies in kidney transplant recipients.

Methods: We searched the PubMed, MEDLINE, Springer, Elsevier Science Direct, Cochrane Library and Google Scholar up to May 2014. Risk ratio (RR) or weighted mean difference (WMD) and their 95 % confidence intervals (CIs) were calculated in fixed-effects model or random-effects model when appropriate. Besides, sensitivity analysis was performed based on the addition of sirolimus in initial immunosuppression protocols.

Results: Total seven studies with 1071 kidney transplant recipients received CNIs withdrawal therapy (experimental group) and 792 kidney transplant recipients received CNIs continued therapy (control group) were included in the meta-analysis. The overall estimates of acute rejection rate (RR = 1.64, 95 % CI: 1.19-2.27, P = 0.003), mean measured glomerular filtration rate (WMD = 9.50, 95 % CI = 2.96-16.03, P = 0.004), thrombocytopenia (RR = 3.39, 95 % CI: 2.27-5.05, P < 0.00001) and hypertension (RR = 0.56, 95 % CI: 0.40-0.78, P = 0.0006) showed that there were significant differences between the CNIs withdrawal and continued therapies in kidney transplant recipients, while no significant differences were found between groups in survival rate, graft survival rate, diabetes, hypercholesterolemia, hypertriglyceridemia and malignancies. In addition, two studies, in which sirolimus was not used in initial immunosuppression protocol, were excluded in sensitivity analysis and the results were still consistent with the overall analysis.

Conclusions: CNIs withdrawal therapy in kidney transplant recipients could significantly decrease risk of hypertension and improve glomerular filtration rate, accompanying with increased risk of acute rejection and thrombocytopenia, compared with the CNIs continued therapy.