Mammalian Target of Rapamycin Inhibitors Combined With Calcineurin Inhibitors as Initial Immunosuppression in Renal Transplantation: A Meta-analysis

Background. The current standard of care immunosuppressive regimen in kidney transplantation (KT) includes a combination of mycophenolates (MMF/MPA) with a calcineurin inhibitor (CNI). Methods. We designed a systematic review including all randomized clinical trials (RCTs) assessing the outcomes in KT recipients receiving mTORi + CNI compared with regimens containing MMF/MPA or azathioprine with CNI. Results. A total of 24 studies with 7356 participants were included. The comparison between mTORi-CNI and MMF/MPA-CNI did not show differences in acute rejection, mortality, or graft loss rates. Better graft function was observed using MMF/MPA-CNI than using mTORi + CNI, but this difference was not evident when the mTORi was associated with reduced dose CNI in more recent studies with everolimus. Dyslipidemia, lymphoceles, and impaired wound healing were more frequent with mTORi-CNI and diarrhea and leukopenia were more frequent with MMF/MPA-CNI. Viral infections at any time and malignant neoplasia beyond 2 years were less frequent with mTORi-CNI. Rates of discontinuation because of adverse effects in the mTORi groups varied between 17% and 46% compared to 0%-26.6% in MMF/MPA groups. The current use of lower mTORi dosage has decreased the discontinuation rates. Conclusions. Efficacy is similar with mTORi + CNI and MMF/MPA-CNI. The safety profile is the predominant difference between the 2 regimens.