Estimated Glomerular Filtration Rate Decline and Incident Frailty in Older Adults

Abstract

Background and objectives: Low eGFR is known to be associated with frailty, but the association between the longitudinal decline of eGFR and incident frailty in older persons remains to be determined. The objective of this study was to investigate whether a fast decline on eGFR would be associated with incident frailty.

Design, setting, participants, & measurements: Community dwellers, aged ≥70, were included in this secondary analysis of the 5-year Multidomain Alzheimer Preventive Trial (MAPT). eGFR was calculated using CKD-Epidemiology Collaboration equation at baseline and at 6, 12, and 24 months. The lowest quartile of eGFR slope (-4.1 ml/min per 1.73 m2 per yr) defined a fast decline. The frailty phenotype (unintentional weight loss, exhaustion, low physical activity, slow gait, low handgrip strength assessed with a 0-5 score, where higher is worse; a score ≥3 defines frailty) was assessed at baseline, 6, 12, 24, 36, 48, and 60 months. Cox models were used to test the association between fast eGFR decline and incident frailty.

Results: A total of 833 participants were frail neither at baseline nor at 2 years and had appropriate follow-up data. Median (IQR) baseline eGFR was 73 (61-84) ml/min per 1.73 m2. Frailty occurred in 95 (11%) participants between 24 and 60 months. Among them, 31/207 (15%) had fast eGFR decline between baseline and 24 months, and 64/626 (10%) did not. In a Cox model adjusted for demographic variables, cardiovascular comorbidity, C-reactive protein, and baseline eGFR, a fast eGFR decline was associated with incident frailty (HR 1.67, 95% CI 1.03 to 2.71). Sensitivity analyses provided consistent findings.

Conclusions: In community-dwelling older adults with relatively preserved baseline eGFR, a fast eGFR decline is associated with incident frailty.

Trial registration: ClinicalTrials.gov NCT00672685.

Keywords: C-reactive protein; EGFR protein; chronic renal insufficiency; comorbidity; epidermal growth factor; exercise; follow-up studies; frailty; gait; geriatric nephrology; glomerular filtration rate; hand strength; human; independent living; older persons; phenotype; progression of renal failure; proportional hazards models; receptor; weight loss.

Copyright © 2019 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

A fast eGFR decline was defined as the lowest quartile of eGFR slope (more rapid than −4.1 ml/min per 1.73 m2 per yr). Distribution of eGFR slope over 2 years in the MAPT study. GFR was estimated using the CKD–Epidemiology Collaboration equation using serum creatinine measured at baseline and at 6, 12, and 24 months. eGFR slope was calculated using linear regression. The box-and-whiskers plot above the histogram represents the slope of eGFR quartiles and the median (box) and 2.5 and 97.5 percentiles (whiskers). A fast eGFR decline was defined as the lowest quartile of eGFR slope (more rapid than −4.1 ml/min per 1.73 m2 per yr).

Figure 2.

A fast loss of eGFR is associated with incident frailty. Kaplan–Meier curves of the cumulative probability of frailty according to fast eGFR decline in the MAPT study. A fast eGFR decline was defined as the lowest quartile of eGFR slope (more rapid than −4.1 ml/min per 1.73 m2 per yr) over the first 2 years of the MAPT study. Participants with a fast eGFR decline (solid line) were compared with participants without (dashed line). In nonfrail participants both at baseline and at 2 years, frailty incidence was assessed over the three subsequent years. According to Fried phenotype model (19), frailty was defined by the presence of at least three of the following items: weight loss, exhaustion, slow gait, low grip strength, and low physical activity.