Frailty, dialysis initiation, and mortality in end-stage renal disease

In light of the recent trend toward earlier dialysis initiation and its association with mortality among patients with end-stage renal disease, we hypothesized that frailty is associated with higher estimated glomerular filtration rate (eGFR) at dialysis start and may confound the relation between earlier dialysis initiation and mortality.

We examined frailty among participants of the Comprehensive Dialysis Study (CDS), a special study of the US Renal Data System, which enrolled incident patients from September 1, 2005, through June 1, 2007. Patients were followed for vital status through September 30, 2009, and for time to first hospitalization through December 31, 2008. We used multivariate logistic regression to model the association of frailty with eGFR at dialysis start and proportional hazards regression to assess the outcomes of death or hospitalization.

Among 1576 CDS participants included, the prevalence of frailty was 73%. In multivariate analysis, higher eGFR at dialysis initiation was associated with higher odds of frailty (odds ratio [OR], 1.44 [95% CI, 1.23-1.68] per 5 mL/min/1.73 m(2); P < .001). Frailty was independently associated with mortality (hazard ratio [HR], 1.57 [95% CI, 1.25-1.97]; P < .001) and time to first hospitalization (HR, 1.26 [95% CI, 1.09-1.45]; P < .001). While higher eGFR at dialysis initiation was associated with mortality (HR, 1.12 [95% CI, 1.02-1.23] per 5 mL/min/1.73 m(2); P = .02), the association was no longer statistically significant after frailty was accounted for (HR, 1.08 [95% CI, 0.98-1.19] per 5 mL/min/1.73 m(2); P = .11).

Frailty is extremely common among patients starting dialysis in the United States and is associated with higher eGFR at dialysis initiation. Recognition of signs and symptoms of frailty by clinicians may prompt earlier initiation of dialysis and may explain, at least in part, the well-described association between eGFR at dialysis initiation and mortality.