Factors Associated with Frailty and Its Trajectory among Patients on Hemodialysis

Abstract

Background and objectives: Frailty is common among patients on hemodialysis and associated with adverse outcomes. However, little is known about changes in frailty over time and the factors associated with those changes.

Design, setting, participants, & measurements: To address these questions, we examined 762 participants in the A Cohort to Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD cohort study, among whom frailty was assessed at baseline and 12 and 24 months. We used ordinal generalized estimating equations analyses and modeled frailty (on a scale from zero to five possible components) and death during follow-up.

Results: The mean frailty score at baseline was 1.9, and the distribution of frailty scores was similar at each evaluation. However, most participants' scores changed, with patients improving almost as often as worsening (overall change, 0.2 points per year; 95% confidence interval, 0.1 to 0.3). Hispanic ethnicity (0.6 points per year; 95% confidence interval, 0.0 to 1.1) and diabetes (0.7 points per year; 95% confidence interval, 0.3 to 1.0) were associated with higher frailty scores and higher serum albumin concentration with lower frailty scores (-1.1 points per g/dl; 95% confidence interval, -1.5 to -0.7). In addition, patients whose serum albumin increased over time were less likely to become frail, with each 1-g/dl increase in albumin associated with a 0.4-point reduction in frailty score (95% confidence interval, -0.80 to -0.05). To examine the underpinnings of the association between serum albumin and frailty, we included serum IL-6, normalized protein catabolic rate, and patient self-report of hospitalization within the last year in a second model. Higher IL-6 and hospitalization were statistically significantly associated with worse frailty at any point and worsening frailty over time, whereas normalized protein catabolic rate was not independently associated with frailty.

Conclusions: There was substantial year to year variability in frailty scores, with approximately equal numbers of patients improving and worsening. Markers of inflammation and hospitalization were independently associated with worsening frailty. Studies should examine whether interventions to address inflammation or posthospitalization rehabilitation can improve the trajectory of frailty.

Keywords: Adiposity; Follow-Up Studies; Hispanic Americans; Humans; IL6 protein, human; Inflammation; Interleukin-6; Serum Albumin; chronic kidney disease; diabetes mellitus; end-stage renal disease; frailty; functional status; hemodialysis; hospitalization; obesity; physical function; renal dialysis.

Figure 1.

Study flow diagram. Patients with a frailty score or death at 12 or 24 months contributed outcome information during follow-up. HD, hemodialysis.

Figure 2.

Changes in frailty scores between baseline and 12 months and between 12 and 24 months. A shows a histogram of the change in scores from baseline to 12 months. The distribution of change was fairly symmetrical around zero. However, only 35% of patients did not change; more patients changed by one point than stayed the same. B shows frailty score at baseline on the x axis and 12 months on the y axis. The area of the circles is proportional to the number of patients in each point. The diagonal line indicates no change in frailty score, and the shading of the dots and the areas of the graph indicate improving or worsening of frailty. This illustration highlights that change occurred across the spectrum of baseline frailty score. C and D show similar data for changes between 12 and 24 months, and the changes were remarkably similar over the second year of observation.

Figure 2.

Changes in frailty scores between baseline and 12 months and between 12 and 24 months. A shows a histogram of the change in scores from baseline to 12 months. The distribution of change was fairly symmetrical around zero. However, only 35% of patients did not change; more patients changed by one point than stayed the same. B shows frailty score at baseline on the x axis and 12 months on the y axis. The area of the circles is proportional to the number of patients in each point. The diagonal line indicates no change in frailty score, and the shading of the dots and the areas of the graph indicate improving or worsening of frailty. This illustration highlights that change occurred across the spectrum of baseline frailty score. C and D show similar data for changes between 12 and 24 months, and the changes were remarkably similar over the second year of observation.