Significance of Frailty among Dialysis Patients

The construct of frailty has been associated with adverse outcomes among elderly individuals, but the prevalence and significance of frailty among patients with end-stage renal disease have not been established. The aim of the current study was to determine the prevalence and predictors of frailty among a cohort of incident dialysis patients and to determine the degree to which frailty was associated with death and hospitalization. We studied a cohort of 2275 adults who participated in the Dialysis Morbidity and Mortality Wave 2 study, of whom two-thirds met our definition of frailty: a composite construct that incorporated poor self-reported physical functioning, exhaustion/fatigue, low physical activity, and undernutrition. Multivariable logistic regression analysis suggested that older age, female sex, and hemodialysis (rather than peritoneal dialysis) were independently associated with frailty. Cox proportional hazards modeling indicated that frailty was independently associated with higher risk of death (adjusted hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.60–3.15) and with the combined outcome of death or hospitalization (adjusted HR 1.63, 95% CI 1.41–1.87). Frailty is extremely common and is associated with adverse outcomes among incident dialysis patients. Given its prevalence and consequences, increased research efforts should focus on interventions aimed to prevent or attenuate frailty in the dialysis population. Chronic kidney disease (CKD) and ESRD are associated with many of the same clinical manifestations as advanced age in the absence of kidney disease, such as inactivity, loss of muscle mass, comorbid conditions, and decline in physical and cognitive functioning. In the geriatric literature, these clinical manifestations have been identified as important contributors to a “frailty phenotype.”1–4 The degree to which adverse outcomes that are associated with CKD and ESRD are mediated by frailty is unknown. Frailty is a multidimensional construct reflecting the decline in health and functioning observed in the elderly, ultimately resulting in increased risk for disability, hospitalization, institutionalization, and death.1,5 Fried et al.6 developed and validated a screening tool for frailty. The screening criteria consist of weight loss, muscle weakness, fatigue or exhaustion, low physical activity, and slow gait. The presence of three or more of these criteria defines the frailty phenotype. This tool was validated by its ability to predict disability, hospitalization, and mortality among participants of the Cardiovascular Health Study (CHS), a cohort study of 5888 community-dwelling individuals who were ≥65 yr of age at study inception. Because some of the criteria, such as grip strength, may not be readily available to investigators in clinical settings, Woods et al.7 developed a set of measures that could be ascertained by patient report using standard instruments such as the Medical Outcomes Study Short-Form 36-Item Questionnaire (SF-36).8,9 These investigators applied their modified definition of frailty to participants in the Women's Health Initiative Observational Study and found that frailty was associated with poor outcomes, including death, hip fracture, reduced capacity to complete activities of daily living, and hospitalization, even after adjustment for demographic characteristics, health behaviors, other disability, and comorbid conditions.7 Two studies10,11 reported a high prevalence of frailty among elderly individuals with mild to moderate CKD; however, the frailty construct has not previously been applied to the ESRD population. Incorporation of the geriatric construct of frailty into the dialysis care setting has the potential to improve the identification of patients who are at risk for adverse, frailty-associated outcomes and might benefit from interventions designed to improve functioning or prevent decline; therefore, we undertook analyses using data from the US Renal Data System (USRDS) to establish the prevalence and predictors of frailty among incident dialysis patients and to determine the degree to which frailty was associated with death and hospitalization. Results Of the 3931 patients enrolled in the Dialysis Morbidity and Mortality Study (DMMS) Wave 2, 2393 completed the Patient Questionnaire, making it possible to determine whether they were frail. Of these, 75 had missing survival data and 43 were younger than 18 yr; 2275 patients were included in the analytic cohort. Table 1 shows the baseline characteristics for those with and without data related to frailty. Those with available data were slightly younger; had a slightly higher serum albumin concentration; were more likely to be white, to be married, to have completed high school, and to be employed; and were less likely to have a history of stroke or to have Medicaid coverage. Prevalence and Predictors of Frailty Overall, two thirds of the study population met the study definition of frailty (Table 2). Although older age was clearly related to frailty, a significant proportion of patients in the younger age groups were also frail, including 44% of patients who were younger than 40 yr and more than half of patients who were aged 40 to 50 yr. Women were more likely than men to be frail in all age categories. Table 3 shows the results of multivariable analysis of the predictors of frailty. Frailty was more common among patients with comorbid conditions, although the associations reached statistical significance only for diabetes, stroke, and lower serum albumin concentrations. Patients who were on hemodialysis were more likely to be frail than those who were on peritoneal dialysis. Early nephrology referral and predialysis erythropoietin use were not associated with frailty (data not shown), but, among hemodialysis patients, those with a permanent vascular access (fistula or graft) were less likely to be frail (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.51 to 0.98). T