Clinical Outcomes in Kidney Transplant Recipients Receiving Long-Term Therapy With Inhibitors of the Mammalian Target of Rapamycin

Authors

  • F. Cortazar,

    Corresponding author
    1. Division of Nephrology and Hypertension, University of Miami, Miller School of Medicine, Miami, FL
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  • M. Z. Molnar,

    1. Institute of Pathophysiology, Semmelweis University, Budapest, Hungary
    2. Harold Simmons Center for Chronic Disease Research & Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA
    3. Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary
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  • T. Isakova,

    1. Division of Nephrology and Hypertension, University of Miami, Miller School of Medicine, Miami, FL
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  • M. E. Czira,

    1. Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary
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  • C. P. Kovesdy,

    1. Division of Nephrology, Salem VA Medical Center, Salem, VA
    2. Division of Nephrology, University of Virginia, Charlottesville, VA
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  • D. Roth,

    1. Division of Nephrology and Hypertension, University of Miami, Miller School of Medicine, Miami, FL
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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

    1. Division of Nephrology and Hypertension, University of Miami, Miller School of Medicine, Miami, FL
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Myles Wolf, mwolf2@med.miami.edu

These authors contributed equally as co-first authors.

Abstract

Inhibitors of the mammalian target of rapamycin (mTOR), sirolimus and everolimus, reduce the incidence of acute rejection following kidney transplantation, but their impact on clinical outcomes beyond 2 years after transplantation is unknown. We examined risks of mortality and allograft loss in a prospective observational study of 993 prevalent kidney transplant recipients who enrolled a median of 72 months after transplantation. During a median follow-up of 37 months, 87 patients died and 102 suffered allograft loss. In the overall population, use of mTOR inhibitors at enrollment was not associated with altered risk of allograft loss, and their association with increased mortality was of borderline significance. However, history of malignancy was the strongest predictor of both mortality and therapy with an mTOR inhibitor. Among patients without a history of malignancy, use of mTOR inhibitors was associated with significantly increased risk of mortality in propensity score-adjusted (hazard ratio [HR] 2.6; 95% CI, 1.2, 5.5; p = 0.01), multivariable-adjusted (HR 3.2; 95% CI, 1.5, 6.5; p = 0.002) and one-to-one propensity score-matched analyses (HR 5.6; 95% CI 1.2, 25.7; p = 0.03). Additional studies are needed to examine the long-term safety of mTOR inhibitors in kidney transplantation, especially among recipients without a history of malignancy.

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