#2923 Pre-surgery plasma metabolites as predictive biomarkers of arteriovenous fistula maturation outcomes

Abstract Background and Aims Arteriovenous fistulas (AVFs) are the preferred vascular access for hemodialysis patients. However, more than 50% fail to mature into functional accesses. The Manchester Vascular Access Study (MANVAS), a prospective observational study, aimed to investigate the natural history and maturation of AVFs. Previously, we identified nine metabolites in pre-surgery plasma samples that were differentially regulated between successful and failed AVF maturation. Here we assess the potential of these metabolites as predictive biomarkers for AVF maturation outcomes. Method Metabolite data were obtained through untargeted metabolomics analysis of plasma samples collected from patients in MANVAS prior to AVF creation. Successful AVF maturation was defined as either achieving adequate hemodialysis using the newly created AVF or meeting a combination of ultrasound criteria (AVF diameter >4 mm and blood flow ≥500 ml/min) and clinical assessment. Associations between metabolites and other key clinical variables with AVF maturation outcomes were analyzed using Lasso logistic regression. The model performance was evaluated using receiver operating characteristic analysis. Results Our study cohort included 44 patients (26 males, age 68.0 ± 13.4 years, 34 Caucasians, 21 with diabetes), of whom 28 (63.6%) experienced successful AVF maturation. The previously identified nine differential pre-surgery plasma metabolites significantly distinguished AVF maturation outcomes. Using Lasso logistic regression analysis, we were able to reduce the nine metabolites to six that were associated with maturation outcomes. The area under the receiver operating characteristic curve was 0.917 (95% confidence interval: 0.833 to 1.000) (Fig. 1). The metabolites with the greatest influence in the model are linked to cellular bioenergetics and inflammation. Adjustments for clinical and demographic variables did not materially alter the results. Conclusion Six metabolites identified in plasma samples collected prior to AVF creation successfully predicted subsequent vascular access maturation outcomes. If validated in larger studies, these metabolites could aid personalized vascular access planning and inform research into potential novel therapeutic targets.