Patients with end-stage renal disease (ESRD) commonly experience physical frailty, exhibited by reduced functional mobility and muscle weakness. Previous studies have demonstrated that at least 70% of older adults with ESRD receiving hemodialysis have physical frailty. There are strong associations between poor physical status and increased risks of adverse events and mortality in this patient population.
Patients with chronic kidney disease, particularly those with ESRD receiving dialysis, have a high prevalence of a syndrome of adverse metabolic and nutritional derangements, designated as protein energy wasting (PEW). The International Society of Renal Nutrition and Metabolism has proposed four causes of PEW in patients on dialysis: (1) nutrient loss into dialysate; (2) dialysis-related inflammation; (3) dialysis-related hypermetabolism; and (4) loss of residual renal function.
There have been few studies on the combined effects of reduced functional mobility, muscle weakness, and low serum albumin on mortality in hemodialysis patients. Takahiro Shimoda, PT, MS, and colleagues recently conducted a retrospective study to examine the associations of reduced functional mobility, muscle weakness, and low serum albumin, alone and in combination, with all-cause mortality in patents with ESRD receiving hemodialysis. Results of the study were reported in the Journal of Renal Nutrition [2018;28(5):302-308].
The study included 490 patients from a hemodialysis center in Japan who were retrospectively enrolled between July 2010 and October 2016. All patients were undergoing hemodialysis therapy three times a week. The primary outcome of interest was all-cause mortality assessed by death registry at the clinic.
Cox proportional hazard regression analysis was used to calculate the independent prognostic effect of the combination of reduced functional mobility, muscle weakness, and low serum albumin on survival (Combined score). Increases in predictive capacity were calculated by combining the associations of reduced functional mobility, muscle weakness, and low serum albumin in comparison to each component alone based on the receiver-operator characteristic curves, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI).
The final study cohort included 314 hemodialysis patients. Of those, 58.6% (n=184) were men, mean age was 66.4 years, and mean duration on dialysis was 8.0 years. Diabetic nephropathy was the most common cause of ESRD (33.4%), followed by glomerulonephritis (29.9%).
The cohort had a mean Combined score of 4.9; 54.5% had a Combined score of ≥5. There was a significant correlation between higher Combined score and older age (P<.001), higher prevalence rates of diabetic nephropathy (P<.001), peripheral artery disease (P=.021), cerebrovascular accident/transient ischemic attack (P=.003), diabetes (P=.001), congestive heart failure (P=.036), higher comorbidity score (P<.001), lower levels of serum albumin and hemoglobin (P<.001 and P<.026, respectively), lower handgrip strength (P<.001), slow gait speed (P<.001), and impairment in activities of daily living (P<.001).
Follow-up ranged from 0.2 to 6.5 years; during the follow-up period, 56 patients died. Causes of death were infection (n=5), cardiovascular disease (n=22), cancer (n=8), cerebral vascular disease (n=4), other causes (n=4), and unknown causes (n=13). In the higher and lower Combined score groups, the median follow-up periods were 3.2 years and 3.9 years; survival was superior in the lower Combined score group (P<.001).
Following adjustments for age, sex, time on hemodialysis, primary kidney disease, body mass index (BMI), serum hemoglobin, and comorbidity index, the hazard ratio for all-cause mortality in the group with Combined score ≥5 was 3.30 (95% confidence interval [CI], 1.59-6.87; P=.001), compared with that in the group with Combined score <5. The hazard ratio per 1 point increase in the Combined score was 1.24 (95% CI, 1.11-1.39; P<.001). In subgroup analyses, there were consistent associations between higher Combined score and poor prognosis, even following adjustment for patient characteristics.
In a comparison of isolated and combined discrimination abilities of reduced functional mobility, muscle weakness, and low serum albumin with all-cause mortality, the area under the curve was increased by adding the Combined score (serum albumin, activities of daily living, gait speed, and handgrip) to patient characteristics (age, sex, time on dialysis, primary kidney disease, BMI, hemoglobin, and comorbidity index). Both NRI and IDI suggested that the addition of Combined score to patient characteristic improved discrimination of patients at high risk of mortality (NRI: 0.380; 95% CI, 0.096-0.664; P<.001; IDI: 0.29, 95% CI, 0.004-0.055; P=.025).
Study limitations cited by the authors included the single-center design; only evaluating the participants’ Combined scores at baseline; defining malnutrition based on serum albumin alone; the observational nature of the study that prevented the researchers from determining whether interventions to address functional mobility, muscle weakness, and low serum albumin would be effective in improving the prognosis of patients undergoing hemodialysis; and the inability to define the underlying mechanisms affecting the higher mortality risk in patients with reduced functional mobility, muscle weakness, and low serum albumin compared with the other populations.
In conclusion, the researchers said, “Reduced functional mobility, muscle weakness, and low serum albumin are associated with poor prognosis in hemodialysis patients. Furthermore, the combined use of reduced functional mobility, muscle power, and serum albumin increases prognostic discrimination capability compared with each component alone in patients on hemodialysis.”
- Researchers in Japan conducted a retrospective study to examine the associations of reduced functional mobility, muscle weakness, and low serum albumin, in combination and alone, with all-cause mortality in patients undergoing hemodialysis therapy.
- Patients with a high Combined score had a lower cumulative survival rate than those with a low Combined score (hazard ratio,. 3.30; 95% confidence interval, 1.59-6.87; P=.001).
- Adding the Combined score to patient characteristics improved discrimination of patients at high risk of mortality.