Background/Objectives: Protein-energy wasting (PEW) and sarcopenia are common in chronic hemodialysis (HD) patients, leading to numerous complications and increased mortality. This study aimed to compare the reliability of the SARC-F (Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls) and the Malnutrition-Inflammation Score (MIS) in assessing sarcopenia and predicting negative outcomes in HD patients. Methods: This cross-sectional study enrolled 109 HD patients. Nutritional assessments were performed, and blood samples were taken for routine blood laboratory investigations. The MIS was used as a scoring system to represent the severity of PEW, while the SARC-F was applied as an indicator of sarcopenia risk and general functional capacity. A multivariable logistic regression was conducted to analyze the association of several predictors with a negative cross-sectional outcome (death). Results: Patients with SARC-F scores ≥ 4 and MISs ≥ 6 were older, had significantly lower albumin and prealbumin levels, and more severe anemia. They were also more likely to report weight loss and poor appetite. A higher MIS was closely associated with unfavourable nutritional status according to the International Society of Renal Nutrition and Metabolism (ISRNM) criteria for PEW. However, in 71.25% of patients with satisfactory functional capacity (SARC-F scores 0-3), some form of PEW was still observed. After performing logistic regression modelling, only the MIS remained strongly associated with the probability of a negative outcome. Conclusions: The SARC-F alone often did not correspond to an increased sarcopenia risk or clear clinical and biochemical indicators of PEW in HD patients. When assessing nutritional risk in this group, it is recommended to use more detailed tools, such as the MIS, to ensure the accurate identification of those at the highest risk for negative outcomes.
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