Association Between Albuminuria and Glomerular Filtration Rate With Incident Frailty

The association between estimated glomerular filtration rate (eGFR) and albuminuria with incident frailty in generally healthy older individuals is unclear. We investigated whether baseline eGFR or urine albumin-to-creatinine ratio (UACR) are associated with incident frailty and assessed them using 2 separate methods: a modified Fried frailty phenotype (FP), and a deficit accumulation frailty index (FI).

This was a secondary analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) randomized trial cohort, which enrolled independent, healthy, older adults aged ≥65 years in Australia and the USA. Time to incident frailty was analyzed using discrete time survival analysis.

In total, 16,965 participants were included using the FP, mean age was 75.0 ± 4.5 years, median baseline eGFR was 78.6 ml/min per 1.73 m² (interquartile range [IQR]: 67.6-89.5), and the median UACR was 0.80 mg/mmol (0.50-1.50). Data to generate the FI outcomes were available for 12,272 participants. The relationships between eGFR and both incident FP and FI were nonlinear, such that an eGFR < 30 or ≥ 95 ml/min per 1.73 m² was significantly associated with an increased risk of incident frailty. For every doubling of baseline UACR, risk of incident frailty increased by 4% using the FP (hazard ratio [HR]: 1.04, 95% CI: 1.02, 1.07) and the FI (HR: 1.04, 95% confidence interval [CI]: 1.01-1.07).

In older, generally healthy adults, both low and high eGFRs were associated with increased risk of incident frailty. Doubling of UACR, even at low levels, was independently associated with incident frailty.