Long-Term Aspartate Aminotransferase and Aspartate Aminotransferase/Alanine Aminotransferase Ratio Exposure Reflects Risk of Low Skeletal Muscle Mass in Maintenance Hemodialysis: A Real-World Cohort Study.

Abstract

Objective: Low skeletal muscle mass is highly prevalent among patients undergoing maintenance hemodialysis (MHD) and is closely linked to protein-energy wasting and adverse clinical outcomes. Aspartate aminotransferase (AST), a routinely measured enzyme involved in amino acid metabolism, is expressed in skeletal muscle and may reflect muscle metabolic status beyond hepatic injury. However, the association between long-term AST exposure and low skeletal muscle mass in the dialysis population remains unclear.

Methods: In this single-center retrospective cohort study, 266 adult patients undergoing MHD were included. Five-year cumulative exposure to AST, alanine aminotransferase (ALT), and the AST/ALT ratio was quantified using time-weighted averages and median values. Skeletal muscle mass was assessed by bioelectrical impedance analysis. Low skeletal muscle mass was defined as skeletal muscle index < 7.0 kg/m² for men and <5.7 kg/m² for women, according to the Asian Working Group for Sarcopenia 2019 criteria. Multivariable logistic regression was performed to evaluate associations, adjusting for demographic, dialysis-related, and nutritional covariates. Nonlinear relationships were examined using restricted cubic spline models.

Results: The study population consisted of 266 MHD patients (mean age 55.88 ± 14.82 years, 60.9% male). The prevalence of low skeletal muscle mass was 15.0%. Higher 5-year time-weighted average AST levels were independently associated with increased odds of low skeletal muscle mass (adjusted odds ratio [OR], 1.057; 95% confidence interval [CI], 1.009-1.107). Similar associations were observed for median AST levels (adjusted OR, 1.092; 95% CI, 1.024-1.164). The AST/ALT ratio demonstrated stronger associations, particularly for median values (adjusted OR, 3.720; 95% CI, 1.635-8.464). ALT-related metrics were not significantly associated with the outcome. Restricted cubic spline analysis showed no evidence of a nonlinear relationship between cumulative AST exposure and low skeletal muscle mass (P = .768 for nonlinearity), suggesting a linear dose-response relationship.

Conclusions: Long-term elevated AST levels and a higher AST/ALT ratio were independently associated with low skeletal muscle mass in patients undergoing MHD. These routinely available biomarkers may provide additional insight into muscle metabolic status and help identify patients at increased nutritional risk.