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CLINICAL RESEARCH STUDY

Frailty and Chronic Kidney Disease: The Third National Health and Nutrition Evaluation Survey
Emilee R. Wilhelm-Leen, BA,a Yoshio N. Hall, MD,c Manjula K. Tamura, MD, MPH,b Glenn M. Chertow, MD, MPHb
Stanford University School of Medicine, Palo Alto, Calif; bDepartment of Medicine, Division of Nephrology, Stanford University School of Medicine, Palo Alto, Calif; cVAPuget Sound Health Care System and University of Washington, Department of Medicine, Division of Nephrology, Seattle.
a

ABSTRACT BACKGROUND: Frailty is common in the elderly and in persons with chronic diseases. Few studies have examined the association of frailty with chronic kidney disease. METHODS: We used data from the Third National Health and Nutrition Examination Survey to estimate theprevalence of frailty among persons with chronic kidney disease. We created a definition of frailty based on established validated criteria, modified to accommodate available data. We used logistic regression to determine whether and to what degree stages of chronic kidney disease were associated with frailty. We also examined factors that might mediate the association between frailty and chronickidney disease. RESULTS: The overall prevalence of frailty was 2.8%. However, among persons with moderate to severe chronic kidney disease (estimated glomerular filtration rate 45 mL/min/1.73 m2), 20.9% were frail. The odds of frailty were significantly increased among all stages of chronic kidney disease, even after adjustment for the residual effects of age, sex, race, and prevalent chronic diseases.The odds of frailty associated with chronic kidney disease were only marginally attenuated with additional adjustment for sarcopenia, anemia, acidosis, inflammation, vitamin D deficiency, hypertension, and cardiovascular disease. Frailty and chronic kidney disease were independently associated with mortality. CONCLUSION: Frailty is significantly associated with all stages of chronic kidney diseaseand particularly with moderate to severe chronic kidney disease. Potential mechanisms underlying the chronic kidney disease and frailty connection remain elusive. © 2009 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2009) 122, 664-671 KEYWORDS: Body composition; Chronic kidney disease; Frailty

Frailty is described in the geriatric literature as a multidimensionalphenotype that reflects declining physical function and a global vulnerability to adverse outcomes in the setting of stress, such as illness or hospitalization.1-5 Multiple instruments to operationalize a definition of frailty have been created and validated.1 One well-validated index, proposed by Fried and colleagues,4 defines frailty as the presence of 3 or more of 5 criteria: unintentional weight loss,exhaustion, weakness,
Funding: This research was funded by a grant from the Stanford University School of Medicine Medical Scholars Program. Conflict of Interest: None. Authorship: All authors had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Emilee R. Wilhelm-Leen, BA, Stanford University School of Medicine, 780 Welch Road, Suite 106,Palo Alto, CA 94304. E-mail address: ewilhelm@stanford.edu

slow walking speed, and low physical activity.4 By using the criteria of Fried and colleagues, estimates of the prevalence of frailty vary from 7% of persons aged more than 65 years to 40% of persons aged more than 80 years.2-4 Frailty is even more prevalent among persons with diabetes and other chronic debilitating diseases.6 Frailtyas defined by the Fried et al criteria is associated with increased risk of falls, hospitalization, disability, and death.4 Although chronic kidney disease in general and end-stage renal disease in particular are known to be associated with impaired health status and physical function, few studies have examined the association between chronic kidney disease and frailty.7-11 Shlipak et al12 found...
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