Comorbidity, Frailty, and Waitlist Mortality among Kidney Transplant Candidates of All Ages

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.

Implications of Frailty for Peritransplant Outcomes in Kidney Transplant Recipients

“…Together, these studies demonstrate that the association between frailty and pre-transplant mortality is robust across different frailty measures. Frailty assessments may be particularly important where the patient comorbidity burden is lower, in identifying high-risk patients who may not be noticed otherwise 19 . These data also show that some frail ESKD patients can benefit from transplant over chronic dialysis, although how to identify those who will benefit and have acceptance posttransplant outcomes is not yet known.…”

Frailty Prevalence in Younger End-Stage Kidney Disease Patients Undergoing Dialysis and Transplantation

“…Despite the association with age, this study highlights that a substantial burden of frailty exists across all age groups; there is a high prevalence of frailty even among those who are not chronologically older, and irrespective of sex, race/ethnicity, and dialysis type. Unlike their healthy counterparts, younger ESKD patients present with years of cardiovascular disease burden and other comorbidities [21, 45], to the extent that their disease profiles often resemble those of older adults. Their unique medical history along with the physical and emotional burden of undergoing renal replacement therapy (dialysis or KT) can often catalyze the cycle of multisystem dysregulation and propel them into a frail state.…”

“…Frailty, as measured by the PFP, is present in approximately 35–48% among patients undergoing dialysis [12, 13] and is associated with adverse outcomes including falls [14], hospitalizations [15], cognitive impairment [12], and mortality [16-18]. Among kidney transplantation (KT) candidates, frailty is associated with decreased access to KT [19], waitlist mortality [19-21], cognitive impairment [22], and poor health-related quality of life [23]. KT recipients who are frail at the time of admission for transplantation are more likely to experience depressive symptoms [24], poor health-related quality of life [25], longer length of stay [26], delirium [27], delayed graft function [28], reduction in mycophenolate mofetil immunosuppression dose [29], early hospital readmission [30], and mortality [31, 32].…”

Associations between multimorbidity and adverse clinical outcomes in patients with chronic kidney disease: a systematic review and meta-analysis

“…36 Twelve studies expressed effect sizes using multimorbidity as a categorical variable, 16-18 24 26 28 32-34 36 39 40 nine as a continuous variable 15 19-21 25 29 30 35 38 and one as both. 31 One study gave a narrative comparison of groups 23 and two used Kaplan-Meier curves. 27 37 Two studies categorised LTCs into types: both used concordant and discordant as types and one also specified mental health and chronic pain LTCs.…”