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Background: Sarcopenia involves an age-related decline in skeletal muscle mass with functional disability or low muscle strength. Vascular calcification (VC) occurs commonly in patients with chronic kidney disease, in whom it is associated with cardiovascular disease. We aimed to investigate the correlations of low muscle mass with the quantified vascular calcification score (VCS) of the arm of vascular access, as well as whether low muscle mass is associated with the incidence of vascular access failure. Methods: The VCS was measured on non-contrast, arm computed tomography using the Agatston method. The lower muscle mass (LMM) group comprised subjects whose skeletal muscle mass of the lower extremities, as measured using bioelectrical impedance, was lower than the median. Higher VC was defined as a score of 500 or above, corresponding to the highest 40% of VCS. The relationship between LMM and VC was explored using univariate and multivariate logistic regression analyses. Results: Seventy-five patients were included, of whom forty-two (56.0%) were men. The median age was 64 years (interquartile range 58–72 years). Of the 75 patients, 73 satisfied the diagnostic criteria for sarcopenia. The median hemodialysis vintage was 49.4 months (range 32.1–99.2 months). No significant differences were found between the non-LMM and LMM groups in sex, end-stage renal disease etiology, and type of vascular access, although the LMM group showed significantly older age and hemodialysis vintage. LMM presented a significant association with VC (hazard ratio (HR) 3.562; 95% CI, 1.341–9.463; p = 0.011). Upon adjustment for hemodialysis vintage, diabetes, and systolic blood pressure, LMM demonstrated an independent association with VC (HR, 10.415; 95% CI, 2.357–46.024; p = 0.002). The risk of vascular access failure was higher in the LMM group (HR, 3.652; 95%, CI 1.135–11.749; p = 0.03). VC was a full mediator in the relationship of LMM with recurrent vascular access failure. Conclusions: We quantified LMM via bioimpedance analysis and found a heretofore-unreported association between LMM and vascular access failure. LMM increases the risk of VC and has the potential to predict vascular access failure. [ABSTRACT FROM AUTHOR]