Higher cystatin C, but not creatinine, predicts frailty risk in individuals with normal kidney function.

OBJECTIVE: This study investigates the associations of creatinine and cystatin C with frailty risk in individuals with normal kidney function, using data from the Health and Retirement Study (HRS) and the China Health and Retirement Longitudinal Study (CHARLS). METHODS: We used CKD-EPI to estimate glomerular filtration rate based on serum creatinine (eGFRscr) and cystatin C (eGFRcysc), respectively, and an eGFR ≥60 was considered "normal kidney function". Frailty was assessed using a frailty index derived from clinical and functional measures. Cox proportional hazards models were used to evaluate the associations of creatinine and cystatin C with incident frailty, adjusting for demographic, lifestyle, and clinical covariates. RESULTS: Creatinine levels showed no significant association with frailty risk in individuals with normal kidney function across both cohorts. In contrast, cystatin C levels were consistently and significantly associated with an increased risk of frailty in individuals with normal eGFRscr. For each 1-unit increase in cystatin C, the adjusted hazard ratios (HRs) were 2.05 (95% CI: 1.30-3.22) in HRS and 2.12 (95% CI: 1.60-2.82) in CHARLS. Quartile analyses revealed a dose-response relationship, with the highest quartile of cystatin C associated with significantly higher frailty risk compared to the lowest quartile (HRS: HR = 1.34, 95% CI: 1.02-1.76; CHARLS: HR = 1.70, 95% CI: 1.40-2.07). CONCLUSIONS: Higher cystatin C levels, but not creatinine levels, were significantly associated with an increased risk of frailty among individuals with normal kidney function, suggesting that cystatin C may be a useful biomarker for early identification of frailty risk.