title: Risk of metabolic complications in kidney transplantation after conversion to mTOR inhibitor: a systematic review and meta-analysis.
abstract: Mammalian target of rapamycin (mTOR) inhibitors have been used in transplantation with the hope of minimizing calcineurin inhibitor (CNI)-induced nephrotoxicity. However, mTOR inhibitors are also associated with a range of side effects, including metabolic complications. We aimed to determine the risks of metabolic complications after the conversion from CNI to mTOR inhibitor postkidney transplant. A systematic search in PubMed up to September 2013 identified nine relevant trials (a total of 2323 patients). The primary end points were the relative risks (RRs) of new-onset diabetes after transplant (NODAT) and hypercholesterolemia. The overall RRs of NODAT and hypercholesterolemia associated with mTOR inhibitors were 1.32 (95% confidence interval [CI] 0.92-1.87) and 2.15 (95% CI 1.35-3.41), respectively, compared with CNI-based regimen. Subgroup analyses revealed no differences in the incidence of NODAT or hypercholesterolemia between sirolimus- versus everolimus-based regimen, or between early versus late conversion. Analyses of secondary outcomes revealed a higher risk of acute rejection, proteinuria and anemia, but no difference in the risk of opportunistic infections after mTOR inhibitor conversion. In conclusion, the conversion from CNI to mTOR inhibitor in low-to-moderate risk kidney transplant recipients was associated with nonsignificant trend toward increased risk of NODAT and significant increase in hypercholesterolemia, acute rejection, proteinuria and anemia.
authors.affiliation: Department of Medicine, Beth Israel Medical Center, New York, NY.
authors.forename: N
authors.initials: N
authors.lastname: Murakami
authors.forename: L V
authors.initials: LV
authors.lastname: Riella
authors.forename: T
authors.initials: T
authors.lastname: Funakoshi
mesh_terms: D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016030:Kidney Transplantation / Q000009:adverse effects*; D009894:Opportunistic Infections / Q000209:etiology; D018570:Risk Assessment; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Calcineurin inhibitor (CNI); clinical research/practice; complication: medical/metabolic; immunosuppressant; immunosuppression/immune modulation; immunosuppressive regimens; kidney transplantation/nephrology; mechanistic target of rapamycin (mTOR); minimization/withdrawal