Background: Among community-dwelling older adults, frailty is associated with heightened inflammation and subsequent mortality. Although frailty is common among patients on the KT waitlist, the role of frailty and inflammation in this population remains unclear. We quantified the association between frailty, inflammation, and mortality in ESRD patients on the KT waitlist, and tested whether frailty and/or inflammation improves risk prediction beyond clinical factors available in registry-based models.
Methods: We studied 1,975 prevalent ESRD patients on the KT waitlist (11/1/09-2/28/17) in a multi-center cohort study of measured frailty in patients undergoing transplant evaluation; serum inflammatory markers (interleukin-6 [IL-6], soluble tumor necrosis factor-a receptor-1 [sTNFR1], and C-reactive protein [CRP]) were analyzed in 605 of these participants. We compared the C-statistic of an established registry-based prediction model adding frailty and/or inflammation (1SD change in log IL-6, sTNFR1, CRP, or an aggregate inflammatory index).
Results: The mean age was 53.7 and 18.4% were frail. Frail candidates had elevated serum IL-6 (P<0.001), sTNFR1 (P=0.02), CRP (P=0.01), and a higher inflammatory index (P<0.001). The registry-based model had moderate predictive ability (C-statistic=0.655). Frailty was associated with increased waitlist mortality risk (frail HR=2.19, 95%CI:1.26-3.79) (Figure) but did not improve mortality risk prediction (C-statistic=0.646; P=0.65) (Table). Like frailty, IL-6 (HR=2.13, 95%CI:1.41-3.22), sTNFR1 (HR=1.70, 95%CI:1.12-2.59), CRP (HR=1.68, 95%CI:1.06-2.67), and the inflammatory index (HR=2.09, 95%CI:1.38-3.16) were all associated with increased waitlist mortality risk. But unlike frailty, adding IL-6 (C-statistic=0.777; P=0.02), CRP (C-statistic=0.728; P=0.02), or the inflammatory index (C-statistic=0.777; P=0.02) substantially improved mortality risk prediction.
Conclusions: Among adult ESRD patients on the KT waitlist, frailty and inflammation were associated with increased waitlist mortality risk, but only inflammatory markers significantly improved mortality risk prediction. Heightened inflammation may be the biological link between frailty and mortality in KT candidates.