*Purpose: Frailty is associated with poor outcomes like delirium, delayed graft function, and mortality, that may result from inflammation after kidney transplant (KT). Despite a hypothesized underlying pro-inflammatory state, common measures of frailty like the physical frailty phenotype (PFP) do not incorporate inflammatory biomarkers directly. We sought to evaluate the inclusion of inflammatory biomarkers in conjunction with traditional PFP components.

*Methods: We used a 2-center cohort (2009-2017) of KT recipients with measures of PFP and inflammation (IL6, TNFα, C reactive protein [(CRP]) collected at KT. We evaluated construct validity of inflammatory frailty, using latent class analysis, of frailty-inflammatory measures combining PFP (5 components) plus the addition of individual inflammatory biomarkers (highest tertile of IL6, TNFα, CRP, or inflammatory index, separately) as a 6^th component. We used Kaplan-Meier methods and adjusted Cox proportional hazards to assess mortality risk after KT by inflammatory frailty.

*Results: Among 378 KT recipients, five-year survival for each frailty-inflammation index (frail vs nonfrail) was: 81% vs 93% (IL6-frailty), 87% vs 89% (CRP-frailty), and 83% vs 91% (TNFα-frailty). After adjustment, mortality was 2.04-fold higher for IL6-frail recipients compared to non-IL6-frail (95%CI:1.02-4.10, p=0.05); there were no associations between the mortality and the other frailty-inflammatory indices (CRP-frail:1.01,95%CI:0.51-0.98,p=0.9; TNFα-frail:1.94,95%CI:0.98-3.83,p=0.06).

*Conclusions: IL-6 frailty combines biomarkers and physical components that improves upon the physical frailty phenotype and is more strongly associated with post-KT mortality. Measurement of biomarkers at admission for transplantation in addition to the measurement of frailty can guide post-operative risk assessment and patient counseling.

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