title: A systematic review of conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitors for maintenance immunosuppression in kidney transplant recipients.
abstract: This was a systematic review of randomized controlled trials comparing delayed conversion of mammalian target of rapamycin inhibitors (mTORi) for calcineurin inhibitors (CNIs) versus CNI continuation in kidney transplantation. Databases (2000-2012) and conference abstracts (2009-2012) were searched giving a total of 29 trials. Outcomes analyzed included GFR, graft loss, rejection and adverse events and were expressed as weighted mean differences (WMDs) or as risk ratios (RRs). Patients converted to mTORi up to 1 year posttransplant in intention-to-treat analysis had higher GFR compared with those remaining on CNI (WMD 0.28 mL/min/1.73 m(2) , 95% confidence interval [CI] 0.21-0.36; I(2)  = 68%, p < 0.001). Stratifying trials by time posttransplant or type of mTORi did not change the overall heterogeneity. For on-treatment population, mTORi was associated with higher GFR (14.21 mL/min/1.73 m(2) , 10.34-18.08; I(2)  = 0%, p = 0.970) 2-5 years posttransplant. The risk of rejection at 1 year was higher in mTORi trials (RR 1.72, 1.34-2.22; I(2)  = 12%, p = 0.330). Discontinuation secondary to adverse events was more common in patients on mTORi, whereas the incidence of skin cancers and cytomegalovirus infection was lower in patients on mTORi. Conversion from CNI to mTORi is associated with short-term improvements in GFR in a number of studies but longer-term follow-up data of graft and patient survival are required.
authors.affiliation: Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: W H
authors.initials: WH
authors.lastname: Lim
authors.forename: J
authors.initials: J
authors.lastname: Eris
authors.forename: J
authors.initials: J
authors.lastname: Kanellis
authors.forename: B
authors.initials: B
authors.lastname: Pussell
authors.forename: Z
authors.initials: Z
authors.lastname: Wiid
authors.forename: D
authors.initials: D
authors.lastname: Witcombe
authors.forename: G R
authors.initials: GR
authors.lastname: Russ
mesh_terms: D065095:Calcineurin Inhibitors / Q000008:administration & dosage*; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D016032:Randomized Controlled Trials as Topic; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Clinical research; dysfunction; immune modulation; immunosuppression; immunosuppressive regimens; kidney (allograft) function; kidney transplantation; maintenance; meta-analysis; minimization; nephrology; practice; withdrawal