BACKGROUND AND OBJECTIVES: Kidney disease is associated with physiologic changes 
that may predispose to frailty. This study sought to investigate whether lower 
levels of kidney function were associated with prevalent or incident frailty in 
Cardiovascular Health Study (CHS) participants.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: CHS enrolled community-dwelling 
adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent 
frailty, included were 4150 participants without stroke, Parkinson disease, 
prescribed medications for Alzheimer disease or depression, or severely impaired 
cognition. To examine incident frailty, included were a subset of 3459 
participants without baseline frailty or development of exclusion criteria 
during follow-up. The primary predictor was estimated GFR (eGFR) calculated 
using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum 
creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 
4 years of follow-up. Frailty was ascertained on the basis of weight loss, 
exhaustion, weakness, slowness, and low physical activity.
RESULTS: The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 
1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% 
had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ≥90 
ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% 
confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 
4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% 
CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 
60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 
2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty 
whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of 
eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.
CONCLUSIONS: In community-dwelling elders, lower eGFR(cys) was associated with a 
higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. 
These findings highlight the importance of considering non-GFR determinants of 
kidney function.