Frailty, Inflammatory Markers, and Waitlist Mortality Among Patients with End-Stage Renal Disease in a Prospective Cohort Study

BACKGROUNDAmong community-dwelling older adults, frailty is associated with heightened markers of inflammation and subsequent mortality. Although frailty is common among ESRD patients, the role of frailty and markers of inflammation in this population remains unclear. We quantified these associations in patients on the kidney transplant (KT) waitlist and tested whether frailty and/or markers of inflammation improve waitlist mortality risk prediction. METHODSWe studied 1,975 ESRD patients on the KT waitlist (11/1/09-2/28/17) in a multi-center cohort study of frailty. Serum inflammatory markers (interleukin-6 [IL-6], soluble tumor necrosis factor-α receptor-1 [sTNFR1], and C-reactive protein [CRP]) were analyzed in 605 of these participants; we calculated the inflammatory index score using IL-6 and sTNFR1. We compared the C-statistic of an established registry-based prediction model for waitlist mortality adding frailty and/or inflammatory markers (1SD change in log IL-6, sTNFR1, CRP, or inflammatory index). RESULTSThe registry-based model had moderate predictive ability (c-statistic=0.655). Frailty was associated with increased mortality (2.19, 95%CI:1.26-3.79) but did not improve risk prediction (c-statistic=0.646; P=0.65). Like frailty, IL-6 (2.13, 95%CI:1.41-3.22), sTNFR1 (1.70, 95%CI:1.12-2.59), CRP (1.68, 95%CI:1.06-2.67), and the inflammatory index (2.09, 95%CI:1.38-3.16) were associated with increased mortality risk; unlike frailty, adding IL-6 (c-statistic=0.777; P=0.02), CRP (c-statistic=0.728; P=0.02), or inflammatory index (c-statistic=0.777; P=0.02) substantially improved mortality risk prediction. CONCLUSIONFrailty and markers of inflammation were associated with increased waitlist mortality risk, but only markers of inflammation significantly improved ESRD risk prediction. These findings help clarify the accelerated aging physiology of ESRD and highlight easy to measure markers of increased waitlist mortality risk.