Kidney Function Estimation and its Relationship with Frailty in Older Adults: Insights from SHIP-TREND

Background: End-stage renal disease (ESRD) is closely associated with frailty, but the relationship between earlier stages of kidney dysfunction and frailty in the broader older population remains unclear. This study investigates the association between kidney function and frailty in community-dwelling older adults in Northeast Germany, using cross-sectional data from the population-based SHIP-TREND study. Methods: Data of 1,456 community-dwelling participants aged [&ge;]60 years of the SHIP-TREND cohort were analyzed. Frailty was classified using modified Fried phenotype criteria. Kidney function was assessed using various estimated glomerular filtration rate (eGFR) formulas (MDRD, CKD-EPI and EKFC, based on creatinine or cystatin C). Associations between eGFR, and albuminuria and frailty were examined using multivariable linear and logistic regression models adjusted for age, sex, comorbidities, and body composition. Results: Frailty prevalence was 2.3%, and frail individuals had significantly lower eGFR, particularly when calculated using cystatin C-based formulas. CKD-EPI and EKFC equations using cystatin C showed the strongest associations with frailty (e.g. CKD-EPICysC: OR = 31.3, 95 % CI 5.04 - 194.93, p < 0.001 for eGFR <30 vs. [&ge;]60 mL/min/1.73 m{superscript 2}). Creatinine-based equations demonstrated weaker associations, likely due to confounding by muscle mass. Albuminuria was not significantly associated with frailty. Frail participants exhibited higher BMI but lower muscle mass, pointing to sarcopenic obesity as a potential contributor to the pathophysiology linking reduced kidney function and frailty. Conclusion: This study shows that lower kidney function, especially when estimated using cystatin C-based equations, is significantly associated with frailty in older adults. The strength of our study lies in the large, well-defined population and standardized assessments. In clinical practice, incorporating cystatin C into GFR estimation alongside muscle mass assessments may provide a more reliable framework for identifying CKD in older adults, and may also improve the prediction of frailty. Key pointsO_LILower kidney function, especially via cystatin C-based eGFR, is strongly linked to frailty in older adults. C_LIO_LISarcopenic obesity may drive this link, with frail individuals showing high BMI but low muscle mass. C_LIO_LICombining cystatin C-based eGFR with muscle mass assessment may improve CKD detection and frailty prediction in clinical practice. C_LI