Abstract 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. Keywords: Chronic kidney disease, intermuscular adipose tissue accumulation, inflammation, muscle dysfunction

The authors have declared no competing interest.

This study was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01 DK125794), (grant R01 DK101509), the Veterans Administration Merit Award (5I01CX001755), National Heart and Blood Institute (grant 1R01HL155523), (grant 1R01HL157378) and the Clinical Translational Science Award (UL1‐TR000445) from the National Center for Advancing Translational Sciences.

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The Institutional Review Boards of Vanderbilt University Medical Center and Veteran Administration Nashville Campus approved the study protocol, and written informed consent was obtained from all study participants.

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All data produced in the present study are available upon reasonable request to the authors.