María Pérez Fernández1, Patricia Martínez Miguel1, Hao Ying2, Christine E Haugen2, Nadia M Chu3, Diego María Rodríguez Puyol1, Leocadio Rodríguez-Mañas4, Silas P Norman5, Jeremy D Walston6, Dorry L Segev2,3, Mara A McAdams-DeMarco7,8. 1. Department of Nephrology, Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain. 2. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 3. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA. 4. Hospital Universitario de Getafe, Madrid, Spain. 5. Division of Nephrology, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA. 6. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 7. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, mara@jhu.edu. 8. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA, mara@jhu.edu.
Abstract
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.
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.
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