Comorbidity, frailty, and waitlist mortality among kidney transplant candidates of all ages

Background: Kidney transplantation (KT) candidates often present with multiple comorbidities. These patients also have a substantial burden of frailty, which is also associated with increased mortality. However, it is unknown if frailty is merely a surrogate for comorbidity, itself an independent domain of risk, or if frailty and comorbidity have differential effects. Better understanding the interplay between these 2 constructs will improve clinical decision making in KT candidates. Objective: To test whether comorbidity is equally associated with waitlist mortality among frail and nonfrail KT candidates and to test whether measuring both comorbidity burden and frailty improves mortality risk prediction. Methods: We studied 2,086 candidates on the KT waitlist (November 2009 - October 2017) in a multicenter cohort study, in whom frailty and comorbidity were measured at evaluation. We quantified the association between Charlson comorbidity index (CCI) adapted for end-stage renal disease and waitlist mortality using an adjusted Cox proportional hazards model and tested whether this association differed between frail and nonfrail candidates. Results: At evaluation, 18.1% of KT candidates were frail and 51% had a high comorbidity burden (CCI score ≥2). Candidates with a high comorbidity burden were at 1.38-fold (95% CI 1.01-1.89) increased risk of waitlist mortality. However, this association differed by frailty status (p for interaction = 0.01): among nonfrail candidates, a high comorbidity burden was associated with a 1.66-fold (95% CI 1.17-2.35) increased mortality risk; among frail candidates, here was no statistically significant association (HR 0.75, 95% CI 0.44-1.29). Adding this interaction between comorbidity and frailty to a mortality risk estimation model significantly improved prediction, increasing the c-statistic from 0.640 to 0.656 (p < 0.001). Conclusions: Nonfrail candidates with a high comorbidity burden at KT evaluation have an increased risk of waitlist mortality. Importantly, comorbidity is less of a concern in already high-risk patients who are frail.