Unmasking malnutrition through soluble RAGE: A biomarker-guided insight from FRASNET

Background: Malnutrition is a prevalent geriatric syndrome, with multifactorial etiology and consequences for health and independence. Inflammation contributes to nutritional decline, yet conventional inflammatory markers often lack sensitivity for identifying malnutrition risk. The soluble receptor for advanced glycation end-products (sRAGE), a modulator of inflammatory responses, has emerged as a biomarker of disease risk and adverse outcomes in various conditions. Objectives: to evaluate the association between circulating sRAGE levels and nutritional status in community-dwelling older adults. Methods: This prospective observational study was conducted within the FRASNET cohort. Fifty-two community-dwelling older adults underwent multidimensional geriatric assessments during two time periods: 2017-2020 and 2023-2024. Serum sRAGE levels were measured at both timepoints. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF). Associations between sRAGE and clinical parameters were evaluated through linear regression models adjusted for age and sex. The diagnostic performance of sRAGE in identifying malnutrition was assessed using ROC curve analysis. Results: Higher baseline sRAGE levels were significantly associated with lower BMI (β = -0.003, p = 0.036), reduced calf circumference (β = -0.002, p = 0.04), and poorer nutritional status as revealed by MNA-SF scores (β = -0.001, p = 0.03) at follow-up. Associations were more pronounced in women. ROC analysis indicated good diagnostic accuracy for identifying malnutrition risk, with an AUC of 0.85. The optimal sRAGE cut-off value for malnutrition risk was 1362.5 pg/ml. Conclusions: Higher sRAGE levels were prospectively associated with poorer nutritional outcomes in older adults, particularly in women. sRAGE may aid early identification of inflammation-related malnutrition risk.