ArticleInternational urology and nephrology2026
Deficit accumulation frailty and risk of incident chronic kidney disease: a prospective analysis of the UK biobank and CHARLS cohorts.
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Abstract
backgroundFrailty is recognized as a clinical marker of reduced physiological reserve, but its longitudinal impact on renal health across diverse populations remains unclear. We investigated the association between baseline frailty and incident chronic kidney disease (CKD) risk in a European and an East Asian cohort.
methodsWe analyzed data from the UK Biobank (UKB, N = 451,067) and the China Health and Retirement Longitudinal Study (CHARLS, N = 7,013). Frailty was quantified using a deficit-accumulation Frailty Index (FI). Incident CKD was identified via electronic health records in UKB and biochemical testing or self-reports in CHARLS. Cox proportional hazards models and restricted cubic splines (RCS) were used to evaluate risks and dose-response relationships. The proportional hazards assumption was tested using Schoenfeld residuals, and Fine-Gray subdistribution hazard models were performed to account for the competing risk of death. Cumulative risk curves for incident CKD were plotted using the Kaplan-Meier method, and group differences were assessed with the log-rank test. Subgroup analyses were also performed.
resultsOver the median follow-up, frailty was significantly associated with incident CKD risk in both cohorts. In the UKB, hazard ratios (HRs) for pre-frailty and frailty compared to robust individuals were 1.64 (95% CI: 1.59, 1.69) and 2.75 (95% CI: 2.61, 2.89), respectively. In CHARLS, corresponding HRs were 1.45 (95% CI: 1.20, 1.75) and 1.69 (95% CI: 1.35, 2.11). Fine-Gray subdistribution hazard models confirmed the robustness of these findings to the competing risk of death (Table S5). We observed a significant interaction with age in both cohorts, with stronger associations in participants under 65 years.
conclusionFrailty was associated with incident CKD in both cohorts. These findings support the value of frailty assessment for identifying individuals at elevated renal risk, particularly before age 65 years.
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