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Background: Arteriovenous fistula (AVF) failure due to thrombosis is a major cause of morbidity in patients undergoing regular hemodialysis (HD). Advanced glycation end products (AGEs) and their receptor (RAGE) might contribute to inflammation, neointimal hyperplasia, and thrombosis. RAGE has a C-truncated secretory receptor form, called soluble RAGE (sRAGE). In this study, we aimed to evaluate the association of serum sRAGE with AVF failure due to thrombosis in HD patients. Methods: Eighty-eight prevalent HD patients with functional AVF were included in the study. The presence of stenosis, clinical and laboratory data, and serum sRAGE was evaluated at inclusion. sRAGE concentration was measured by a competitive enzyme-linked immunosorbent assay, and stenosis was detected by ultrasound. Patients were prospectively followed up for 36 months. During this period, AVF failure (defined as the absence of blast or palpable thrill and impossible cannulation with 2 needles because of complete thrombosis) was noted and thrombosis was certified by ultrasound examination. Results: During follow-up, 16 (18.18%) patients lost their vascular access due to thrombosis. In multivariate Cox regression analysis, sRAGE was a significant predictor of vascular access thrombosis (hazard ratio = 1.15, 95% confidence interval: 1.03–1.25, p = 0.012). Kaplan-Meier analysis showed a significantly lower AVF patency time in patients with sRAGE >16.78 ng/mL than those with sRAGE <16.78 ng/mL (p = 0.02). In the subgroup of patients with stenosis at baseline, sRAGE, serum albumin, obesity, and ischemic heart disease were associated with thrombosis. Conclusion: In our study, baseline, systemic sRAGE is associated with the occurrence of thrombosis of AVF, and this marker has a significant impact on AVF survival. [ABSTRACT FROM AUTHOR]