The association between serum indoxyl sulfate and radial-cephalic arteriovenous fistulas dysfunction in ESKD patients: a prospective study

Radial-artery to cephalic-vein end-to-side arteriovenous fistulae (RCAVF) are the first-line vascular access for hemodialysis, yet early stenosis or thrombosis reduces its long-term patency. Indoxyl sulfate (IS), a protein-bound uremic toxin with diverse vascular effects, may impede fistula maturation. We conducted a single-center prospective cohort study enrolling 113 stage 5 chronic kidney disease patients who underwent RCAVF creation between February 2023 and August 2024. Patients were stratified by IS tertiles to assess fistula outcomes. Multivariable Cox regression, Kaplan-Meier analyses, and nomogram construction were used to identify risk factors and patency. Additionally, multiplex tyramide signal amplification immunofluorescence was applied to 40 samples of cephalic vein to quantify aryl hydrocarbon receptor (AHR) and tissue factor (TF) expression. After a median follow-up of 12 months, serum IS was higher in the dysfunction group (<i>p</i> = 0.005). Elevated IS (<i>p</i> = 0.013) and diabetes mellitus (<i>p</i> = 0.006) were independent risk factors for RCAVF dysfunction. Restricted cubic spline analysis showed a linear relationship between IS and risk. Kaplan-Meier curves revealed decreasing primary patency with increasing IS tertiles (<i>p</i> < 0.05), consistent in diabetic patients. The 1-year patency nomogram had good predictive performance (AUC = 0.87). Histopathology showed upregulated AHR and TF expression in veins from dysfunctional fistulas, with correlated fluorescence intensities (<i>r</i> = 0.60, <i>p</i> < 0.05), though neither correlated directly with serum IS (<i>p</i> > 0.05). In conclusion, elevated serum IS independently predicts RCAVF dysfunction, and the aberrant IS-AHR-TF signaling axis may contribute to its pathogenesis.