A prospective study of frailty in nephrology-referred patients with CKD

Background: Frailty is a construct developed to characterize a state of reduced functional capacity in older adults. However, there are limited data describing the prevalence or consequences of frailty in middle-aged patients with chronic kidney disease (CKD). Study Design: Observational study. Setting & Participants: 336 non-dialysis-dependent patients with stages 1-4 CKD with estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m² (by the CKD-EPI [CKD Epidemiology Collaboration] serum creatinine-based equation) or evidence of microalbuminuria enrolled in the Seattle Kidney Study, a clinic-based cohort study. Findings were compared with community-dwelling older adults in the Cardiovascular Health Study. Outcome: Prevalence and determinants of frailty in addition to its association with the combined outcome of all-cause mortality or renal replacement therapy. Measurements: We defined frailty according to established criteria as 3 or more of the following characteristics: slow gait, weakness, unintentional weight loss, exhaustion, and low physical activity. We estimated kidney function using serum cystatin C concentrations (eGFR_cys) to minimize confounding due to relationships of serum creatinine levels with muscle mass and frailty. Results: The mean age of the study population was 59 years and mean eGFR_cys was 51 mL/min/1.73 m². The prevalence of frailty (14.0%) was twice that of the much older non-CKD reference population (P < 0.01). The most common frailty components were physical inactivity and exhaustion. After adjustment including diabetes, eGFR_cys categories of <30 and 30-44 mL/min/1.73 m² were associated with a 2.8- (95% CI, 1.3-6.3) and 2.1 (95% CI, 1.0-4.7)-fold greater prevalence of frailty compared with GFR _cys <60 mL/min/1.73 m². There were 63 events during a median 987 days of follow-up. After adjustment, the frailty phenotype was associated with an estimated 2.5 (95% CI, 1.4-4.4)-fold greater risk of death or dialysis therapy. Limitations: Cross-sectional study design obscures inference regarding temporal relationships between CKD and frailty. Conclusions: Frailty is relatively common in middle-aged patients with CKD and is associated with lower eGFR_cys and increased risk of death or dialysis therapy.