journal articles
HIGHER CYSTATIN C, BUT NOT CREATININE, PREDICTS FRAILTY RISK IN INDIVIDUALS WITH NORMAL KIDNEY FUNCTION
Fan Zhang, Yue Xing, Yan Bai, Liuyan Huang, Yifei Zhong
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.
CITATION:
Fan Zhang ; Yue Xing ; Yan Bai ; Liuyan Huang ; Yifei Zhong ; ; (2026): Higher cystatin C, but not creatinine, predicts frailty risk in individuals with normal kidney function. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.1016/j.tjfa.2026.100195