We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01–4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.

OBJECTIVES To understand the natural history of frailty after an aggressive surgical intervention, kidney transplantation (KT). DESIGN Prospective cohort study (December 2008–March 2014). SETTING Baltimore, Maryland. PARTICIPANTS Kidney transplantation recipients (N = 349). MEASUREMENTS The Fried frailty score was measured at the time of KT and during routine clinical follow-up. Using a Cox proportional hazards model, factors associated with improvements in frailty score after KT were identified. Using a longitudinal analysis, predictors of frailty score changes after KT were identified using a multilevel mixed-effects Poisson model. RESULTS At KT, 19.8% of recipients were frail; 1 month after KT, 33.3% were frail; at 2 months, 27.7% were frail; and at 3 months, 17.2% were frail. On average, frailty scores had worsened by 1 month (mean change 0.4, P < .001), returned to baseline by 2 months (mean change 0.2, P = .07), and improved by 3 months (mean change −0.3, P = .04) after KT. The only recipient or transplant factor associated with improvement in frailty score after KT was pre-KT frailty (hazard ratio = 2.55, 95% confidence interval (CI) = 1.71–3.82, P < .001). Pre-KT frailty status (relative risk (RR) = 1.49, 95% CI = 1.29–1.72, P < .001), recipient diabetes mellitus (RR = 1.26, 95% CI = 1.08–1.46, P = .003), and delayed graft function (RR = 1.22, 95% CI = 1.04–1.43, P = .02) were independently associated with long-term changes in frailty score. CONCLUSION After KT, in adult recipients of all ages, frailty initially worsens but then improves by 3 months. Although KT recipients who were frail at KT had higher frailty scores over the long term, they were most likely to show improvements in their physiological reserve after KT, supporting the transplantation in these individuals and suggesting that pretransplant frailty is not an irreversible state of low physiological reserve.

These data suggest that for patients manifesting early severe AMR, splenectomy plus eculizumab may provide an effective intervention for rescuing and preserving allograft function.