Association of eGFR Discrepancy With Subsequent Frailty in Middle-Aged and Older Adults

Background Creatinine- and cystatin C-based estimated glomerular filtration rate estimates are influenced by different non-GFR determinants. Their difference (eGFRcys−eGFRcr) may therefore provide information beyond either marker alone. We examined its longitudinal association with frailty and exploratory indirect associations through grip strength. Methods We analyzed 15,309 observations from 11,174 China Health and Retirement Longitudinal Study participants aged 45 years or older across 2011–2013 and 2015–2018. Standardized eGFR discrepancy was the exposure; follow-up outcomes were the 32-item Frailty Index and frailty (Frailty Index ≥0.25). Linear mixed models and generalized estimating equations accounted for repeated observations. Model 3 was primary; eGFRcys adjustment was a conditional sensitivity analysis. Results Median age was 60.0 years, and 53.4% of participants were female. A 1-SD higher discrepancy was associated with a lower follow-up Frailty Index (β, −0.503; 95% CI, −0.678 to −0.328; P < 0.001) and lower odds of frailty (OR, 0.851; 95% CI, 0.804–0.900; P < 0.001). Associations persisted after eGFRcys adjustment. Exploratory three-wave analyses showed indirect associations through grip strength, not causal mediation. Conclusions Higher eGFR discrepancy was longitudinally associated with lower subsequent frailty burden. Further studies are needed to clarify its clinical interpretation and underlying determinants.