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

Abstract

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 m(2) (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 m(2). 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 m(2) 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 m(2). 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.

Figure 1

CONSORT diagram of Seattle Kidney Study participants included in this study. Abbreviations: GFR = Glomerular filtration rate (estimated by the serum creatinine-based CKD-EPI equation and given in ml/min/1.73m²), UACR = Urine albumin-creatinine ratio.

Figure 2

(a) Prevalence of frailty and intermediate frailty by estimated glomerular filtration rate (eGFR) calculated from serum cystatin C concentration. (b) Prevalence of frailty by eGFR and urine albumin excretion (p-for-interaction=0.06). Error bars represent 95% confidence interval. Numbers under each bar graph represents number of frail subjects over total in each category of cystatin C-based eGFR and albuminuria (<300mg/g versus ≥300mg/g).

Figure 3

Disability according to frailty status. Numbers under each bar represent number of each disability. Abbreviations: ADL = activities of daily living, IADL = instrumental activities of daily living.

Figure 4

Forest plot of adjusted hazard ratios for death or dialysis comparing individual frailty components to the frailty phenotype and co-morbidities. Error bars represent 95% confidence interval. Estimated hazard ratios are adjusted for age, sex, BMI, diabetes, cardiovascular disease, and eGFR_cys (cystatin C-based estimated glomerular filtration rate). DM = diabetes mellitus; CVD = cardiovascular disease.