Bongetti, Elisa K (EK);Wilkinson, Anna L (AL);Wetmore, James B (JB);Murray, Anne M (AM);Woods, Robyn L (RL);Espinoza, Sara (S);Ernst, Michael E (ME);Fravel, Michelle A (MA);Orchard, Suzanne G (SG);Phuong Thao, Le Thi (LT);Ryan, Joanne (J);Wolfe, Rory (R);Polkinghorne, Kevan R (KR);

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Kidney Int Rep.2024 Nov 18;10(2):489-502.doi:10.1016/j.ekir.2024.11.017

Abstract

INTRODUCTION: 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).

METHODS: 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.

RESULTS: 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 m (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 m 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).

CONCLUSION: 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.