Combined Assessment of Skeletal Muscle Mass Index and Extracellular-to-Intracellular Water Ratio Predicts Mortality and Health-Related Quality of Life in Hemodialysis Patients

Background: Decreased skeletal muscle mass is common in hemodialysis patients and contributes to adverse outcomes. However, muscle mass alone does not fully capture muscle health. An imbalance between extracellular and intracellular water (ECW/ICW ratio) may reflect tissue-level integrity of skeletal muscle. This study examined the combined prognostic significance of the skeletal muscle mass index (SMI) and ECW/ICW ratio for mortality and health-related quality of life (HRQoL) in hemodilaysis patients. Methods: In this multicenter cohort study, 295 maintenance hemodialysis patients (208 men, 87 women) underwent multifrequency bioelectrical impedance analysis. Low SMI was defined according to the Asian Working Group for Sarcopenia (men <7.0 kg/m 2 , women <5.7 kg/m 2 ), and high ECW/ICW was defined as ≥0.66. Patients were categorized into four groups based on SMI and ECW/ICW status. HRQoL was assessed using the Kidney Disease Quality of Life Short Form, and mortality was recorded through March 2024. Results: Among the cohort, 93 patients (31.5%) had low SMI, and 38 (12.9%) had both low SMI and high ECW/ICW. These patients were older and demonstrated lower ICW, poorer nutritional status, chronic inflammation, and higher natriuretic peptide levels. During a median follow-up of 3.7 years, 34 patients died. Low SMI (HR 1.82, 95% CI 1.11–3.65) and high ECW/ICW (HR 2.21, 95% CI 1.34–4.08) independently predicted mortality, while their coexistence conferred the highest risk (HR 3.95, 95% CI 2.01–7.72). Both indices were associated with impaired HRQoL across multiple domains, particularly those related to physical functioning. Conclusions: Combined assessment of SMI and ECW/ICW identifies muscle vulnerability and predicts mortality and HRQoL in hemodialysis patients. This simple, noninvasive approach may improve early detection of high-risk individuals and inform targeted interventions addressing nutrition, inflammation, and fluid management.