The Association Between Circulating Myostatin and Skeletal Muscle Mass Varies by Nutritional–Inflammatory Status in Hemodialysis Patients

Myostatin (MSTN) is a negative regulator of skeletal muscle growth. However, previous studies in hemodialysis patients have reported inconsistent associations between circulating MSTN and muscle-related parameters, and the reasons for these discrepancies remain unclear. This cross-sectional study aimed to investigate whether these associations varied across nutritional and inflammatory contexts. We enrolled 138 maintenance hemodialysis patients. Serum MSTN levels were measured by ELISA, and skeletal muscle index (SMI), handgrip strength (HGS), and sarcopenia were assessed according to AWGS 2025 criteria. Nutritional and inflammatory status were evaluated using the Nutritional Risk Index for Japanese hemodialysis patients (NRI-JH) and C-reactive protein (CRP), respectively. In the overall cohort, higher serum MSTN levels were associated with greater SMI and HGS. In exploratory analyses, a significant negative three-way interaction among MSTN, NRI-JH, and CRP was observed for SMI (B = −0.445, p = 0.018). Above the model-derived Johnson–Neyman boundary of CRP (0.22 mg/dL), the positive association between MSTN and SMI was progressively weaker with increasing NRI-JH scores. These findings suggest statistical heterogeneity in the association between circulating MSTN and skeletal muscle mass across nutritional–inflammatory backgrounds in hemodialysis patients. However, the results are exploratory and require validation in larger independent cohorts.