Inhibitors of mTOR and Risks of Allograft Failure and Mortality in Kidney Transplantation

Authors

  • T. Isakova,

    1. The Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
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    • Contributed equally.

  • H. Xie,

    1. The Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, FL
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    • Contributed equally.

  • S. Messinger,

    1. The Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, FL
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  • F. Cortazar,

    1. The Department of Medicine, Massachusetts General Hospital, Boston, MA
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  • J. J. Scialla,

    1. The Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
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  • G. Guerra,

    1. The Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
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  • G. Contreras,

    1. The Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
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  • D. Roth,

    1. The Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
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  • G. W. Burke III,

    1. Department of Surgery, University of Miami Miller School of Medicine, Miami, FL
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  • M. Z. Molnar,

    1. Harold Simmons Center for Chronic Disease Research & Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA
    2. Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
    3. Institute of Pathophysiology, Semmelweis University, Budapest, Hungary
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  • I. Mucsi,

    1. Institute of Pathophysiology, Semmelweis University, Budapest, Hungary
    2. Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary
    3. Department of Medicine, Division of Nephrology, McGill University Health Centre, Montreal, Quebec, Canada
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  • M. Wolf

    Corresponding author
    • The Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
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Myles Wolf, mwolf2@med.miami.edu

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.

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