title: Inhibitors of mTOR and risks of allograft failure and mortality in kidney transplantation.
abstract: Data on long-term outcomes of users of inhibitors of the mammalian target of rapamycin (mTORI) are lacking in kidney transplantation. In an analysis of 139 370 US kidney transplant recipients between 1999 through 2010, we compared clinical outcomes among users of mTORIs versus calcineurin inhibitors (CNI) in their primary immunosuppresive regimen. During the first 2 years posttransplantation, primary use of mTORIs without CNIs (N = 3237) was associated with greater risks of allograft failure and death compared with a CNI-based regimen (N = 125 623); the hazard ratio (HR) of the composite outcome ranged from 3.67 (95% confidence interval [CI], 3.12-4.32) after discharge to 1.40 (95% CI 1.26-1.57) by year 2. During years 2-8, primary use of mTORIs without CNIs was independently associated with greater risks of death (HR 1.25; 95% CI, 1.11-1.41) and the composite (HR 1.17; 95%CI, 1.08-1.27) in fully adjusted analyses. The results were qualitatively unchanged in subgroups defined by medical history, immunological risk and clinical course during the index transplant hospitalization. In a propensity-score matched cohort, use of mTORIs was associated with significantly worse outcomes during the first 2 years and greater risks of death (HR 1.21; 95% CI, 1.05-1.39) and the composite (HR 1.18; 95% CI, 1.08-1.30) in years 2-8. Compared with CNI-based regimens, use of an mTORI-based regimen for primary immunosuppression in kidney transplantation was associated with inferior recipient survival.
authors.affiliation: The Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, FL, USA.
authors.forename: T
authors.initials: T
authors.lastname: Isakova
authors.forename: H
authors.initials: H
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Messinger
authors.forename: F
authors.initials: F
authors.lastname: Cortazar
authors.forename: J J
authors.initials: JJ
authors.lastname: Scialla
authors.forename: G
authors.initials: G
authors.lastname: Guerra
authors.forename: G
authors.initials: G
authors.lastname: Contreras
authors.forename: D
authors.initials: D
authors.lastname: Roth
authors.forename: G W
authors.initials: GW
authors.lastname: Burke
authors.forename: M Z
authors.initials: MZ
authors.lastname: Molnar
authors.forename: I
authors.initials: I
authors.lastname: Mucsi
authors.forename: M
authors.initials: M
authors.lastname: Wolf
mesh_terms: D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014481:United States
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases