Frailty mediates the relationship between kidney function measures and all-cause mortality among middle-aged and...

Chronic kidney disease (CKD) and frailty are prevalent conditions in middle-aged and older adults; both are independently associated with an increased mortality risk. However, the interrelationship between kidney function, frailty, and mortality in individuals aged 45 years and older remains incompletely understood. We conducted a cross-sectional analysis of frailty prevalence and a longitudinal analysis of mortality outcomes using data from 9079 participants aged ≥45 years from the National Health and Nutrition Examination Survey (2007-2018). Kidney function was assessed by estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), and CKD status. Frailty was defined using a modified Fried phenotype. All-cause mortality was determined through National Death Index linkage. Frailty prevalence was 15.7%. CKD prevalence, lower eGFR, and higher ACR were associated with higher odds of frailty. During a median follow-up of 77 months (interquartile range: 35-117 months), 18.8% of participants died. Impaired kidney function, as defined by reduced eGFR, elevated ACR, or the presence of CKD, was associated with a higher mortality risk, particularly among frail participants. Frailty mediated approximately 4% of the association between ACR/CKD and mortality. Impaired kidney function is significantly associated with frailty. The association between impaired kidney function and mortality differed descriptively across frailty strata. Frailty mediated a portion of this association, highlighting its importance in the clinical management of individuals with impaired kidney function.