Rapamycin and human longevity among kidney transplant recipients surviving the first year

Abstract Rapamycin, an mTOR inhibitor, continues to be investigated for hypothesized physiological, disease prevention, and longevity benefits, but few studies have been conducted in humans. Using US national organ transplant registry data, one of the largest real-world datasets examining chronic rapamycin exposure in humans, we compared the Kaplan-Meier survival age distribution of 4885 kidney transplant recipients prescribed rapamycin compared to 6589 recipients not prescribed rapamycin. Recipients were followed a median of 11 years and 6443 died during the study period. Propensity score weighting was used to adjust for exposure group differences in age, BMI, diabetes, and 15 other factors. After adjusting for demographic and clinical differences between groups, the median survival age of 64.6 years in the rapamycin group and 64.3 years in the non-rapamycin group were statistically similar (95% confidence interval for median survival age difference −1.6, 2.0 years). In this large cohort of kidney transplant recipients who were alive with a functioning graft at 1 year post-transplant, we did not observe a meaningful improvement in long-term survival with mTOR inhibition.