Differential Associations of Lipopolysaccharide, Soluble NOX2-Derived Peptide, and Hydrogen Peroxide with Adiposity and Muscularity in Adults on Maintenance Hemodialysis

Background: Endotoxemia and oxidative stress may contribute to adverse body-composition changes in patients receiving maintenance hemodialysis, but their relationships with adiposity and muscularity remain incompletely defined. We investigated whether the concentrations of circulating lipopolysaccharide (LPS), soluble NOX2-derived peptide (sNox2-dp), and hydrogen peroxide (H2O2) showed differential associations with bioimpedance-derived body-composition compartments and explored their relationships with normalized protein catabolic rate (nPCR), a surrogate of protein intake. Methods: In this observational, cross-sectional study, adult patients receiving maintenance hemodialysis were enrolled at a single center. Serum LPS and sNox2-dp and H2O2 concentrations were measured before dialysis. Body composition was assessed by bioimpedance analysis; fat mass (FM) was used as an index of adiposity, whereas intracellular water indexed to height squared (ICW/h2) was used as a proxy of muscularity. Associations were examined using Spearman correlation and multivariable linear regression adjusted for age, sex, and nPCR. Results: A total of 58 participants were included with a median age of 73 years; 64% were male and mean body mass index was 24.6 ± 4.2 kg/m2. LPS correlated with sNox2-dp (rho = 0.420, p = 0.001), whereas sNox2-dp correlated with H2O2 (rho = 0.352, p = 0.007); the LPS–H2O2 association was borderline (rho = 0.259, p = 0.050). sNox2-dp correlated positively with fat-free mass, total body water, ICW, and ICW/h2, whereas LPS correlated with FM (rho = 0.305, p = 0.023). Participants with nPCR > 0.89 g/kg/day had higher LPS concentrations than those with lower nPCR (p = 0.015), and nPCR correlated with ICW/h2 (rho = 0.36, p = 0.007). In multivariable analysis, LPS remained independently associated with FM (β = 0.210, p = 0.046). nPCR was positively associated with ICW/h2 at the threshold of statistical significance (β = 1.393, p = 0.050), whereas sNox2-dp showed a nonsignificant positive trend (p = 0.060). Conclusions: In maintenance hemodialysis, endotoxemia and NOX2 activation showed differential associations with body composition: LPS with adiposity and sNox2-dp with muscularity. Higher nPCR was associated with both greater muscularity and higher LPS concentrations, suggesting a complex relationship between protein intake, the gut–oxidative-stress axis, and body composition.