Everolimus With Low-dose Calcineurin Inhibitor Regimens For Kidney Transplant Recipients:A Systematic Review And Meta-analysis

Objective: To evaluate the efficacy and safety of everolimus(EVR)plus low-dose calcineurin inhibitor(CNI)versus mycophenolate mofetil(MMF)plus standard-dose CNI regimen after kidney transplantation(KT).Methods: We searched PUBMED,EMBASE,Clinical Trials.gov,Cochrane Central Register of Controlled Trials,CBM and CNKI databases for randomized controlled trials(RCTs)comparing the outcomes of EVR plus low-dose CNI and MMF plus standard-dose CNI regimen after KT and identified eligible RCTs according to the strict inclusion and exclusion criteria.Assessing the quality of included studies based on Jadad scale and performed a meta-analysis using Rev Man5.3.Result: Eleven RCTs with 2238 renal transplant recipients were included.This meta-analysis presented the following results:(1)EVR plus low-dose CNI regimen was associated with comparable renal function(8RCT,SMD0.16,95% CI(�0.03,0.35),p = 0.09)and a similar rate of acute rejection(RR 1.16,95% CI(0.96,1.42),p = 0.13),graft loss(RR 0.89,95% CI(0.63,1.24),p = 0.49)and mortality(RR 1.19,95% CI(0.69,2.08),p = 0.53)compared to MMF plus standard-dose CNI regimen;(2)EVR plus low-dose Cs A regimen can improve the glomerular filtration rate(GFR)(5RCT,SMD 0.33,95%CI(0.11,0.56),p=0.003),with no increase of the rate of acute rejection(7RCT,RR 0.95,95%CI(0.73,1.22),p=0.67),graft loss(7RCT,RR 1.00,95%CI(0.61,1.63),p=1.00)and mortality(7RCT,RR 0.98,95%CI(0.46,2.11),p=0.96);(3)EVR plus low-dose TAC regimen was associated with a higher risk of acute rejection(3RCT,RR 1.49,95%CI(1.08,2.05),p=0.01),with comparable renal function(2RCT,SMD-0.14,95%CI(-0.65,0.37),p=0.58)and similar rate of graft loss(3RCT,RR 0.63,95%CI(0.36,1.09),p=0.10)and mortality(3RCT,RR 1.21,95%CI(0.51,2.87),p=0.67);(4)In terms of adverse events,EVR plus low-dose CNI regimen could reduce the rate of infection and cytomegalovirus,although the opposite effects were seen for hyperlipidemia,anemia,peripheral,stomatitis,and oral ulcers.Conclusion: EVR plus low-dose CNI regimen was not inferior to MMF plus standard-dose CNI regimen after KT.which when EVR plus low-dose Cs A regimen,not only can reduce acute rejection rate but also had protective effects on renal function.It is a more optimized immunotherapy with efficacy and safety.But when EVR plus low-dose Cs A regimen,it may increase the risk of acute rejection and cautious is needed in clinical.