BACKGROUND AND AIMS: Sarcopenia, defined as a loss in muscle mass and strength, is common in patients with advanced chronic kidney disease (CKD), leading to poor outcomes. Intermuscular adipose tissue (IMAT) accumulation is associated with metabolic and functional abnormalities in chronic disease conditions. This study assesses IMAT in maintenance hemodialysis (MHD) patients and its association with metabolic markers and physical performance. METHODS AND RESULTS: We performed a cross-sectional study comparing MHD patients with controls. IMAT accumulation was measured by analyzing the fat-to-muscle ratio of the calf muscles through Magnetic Resonance Imaging (MRI) scans. Body composition and metabolic markers were assessed (hs-CRP, TNF-α, IL-6, and insulin resistance). Circulating cell-free mitochondrial DNA (ccf-mtDNA) was quantified using qRT-PCR. Muscle function was evaluated with handgrip strength. Inverse propensity weighted (IPW) method was used to test the difference between IMAT levels of the groups. Twenty-five MHD patients and 23 controls were analyzed. The MHD group had higher IMAT accumulation than controls (p <
0.01). IMAT was positively correlated with Body Mass Index (BMI) and fat mass index (FMI) in controls. MHD patients exhibited elevated TNF-α, IL-6, and hs-CRP levels (p <
0.01). Positive correlations were found between IMAT and IL-6 in MHD patients and between IMAT and TNF-α in controls. Handgrip strength was negatively correlated with IMAT in the entire cohort (p <
0.01). CONCLUSION: Our findings highlight the potential role of IMAT in muscle catabolism and functional decline in advanced CKD. Targeting IMAT could be a valuable strategy for improving health outcomes in this population.