Background: A number of studies have provided information regarding the risks and benefits of mammalian target\nof rapamycin inhibitors (mTOR-I) combined with calcineurin inhibitors (CNI) versus mycophenolic acid (MPA).\nMethods: Medline, Embase and the Cochrane Central Register of Controlled Trials were searched. Randomized\ncontrolled trials comparing mTOR-I to MPA as the primary immunosuppressive regimen in combination with CNI\nwere selected and meta-analyzed.\nResults: Eleven randomized controlled trials consisting of 4930 patients in total were included. No significant\ndifference was observed in the risk of biopsy-proven acute rejection and patient death between the two groups.\nHowever, an increased risk of graft loss (relative risk (RR) = 1.20) and inferior graft function (creatinine clearance,\nweighted mean difference (WMD) = ?2.41 ?mol/L) were demonstrated in mTOR-I-treated patients. Patients treated\nwith mTOR-I had a higher risk of new-onset diabetes mellitus (RR = 1.32), dyslipidemia, proteinuria (RR = 1.79), peripheral\nedema (RR = 1.34), thrombocytopenia (RR = 1.97) and lymphocoele (RR = 1.80), but a lower risk of cytomegalovirus\ninfection (RR = 0.40), malignancy (RR = 0.64) and leucopenia (RR = 0.43). There was no difference in diarrhea, anemia,\nurinary tract infection, polyoma virus infection and impaired wound healing when mTOR-I was compared with MPA.\nConclusions: mTOR-I showed no particular superiority to MPA. Notably, mTOR-I had an increased risk of graft loss\nwhen combined with CNI, even when combined with a reduced dose of CNI. Therefore, the optimal dosage strategies\nfor mTOR-I and CNI need to be further explored.
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