Metabolomics analysis identifies pre-surgery plasma metabolites associated with arteriovenous fistula maturation...

Arteriovenous fistulas are the preferred vascular access for most hemodialysis patients; however, poor maturation rates limit their widespread adoption. Here, we investigated plasma metabolites as potential biomarkers associated with fistula maturation outcomes before fistula creation.

We conducted untargeted metabolomics on plasma samples collected before fistula creation surgery in patients from the Manchester Vascular Access Study, a prospective observational study of the natural history of newly created fistulas. Successful fistula maturation was defined as either adequate hemodialysis using the newly created fistula, or a combination of ultrasound criteria (fistula diameter >4 mm with a blood flow ⩾ 500 mL/min) and clinical assessment. Metabolomics data were analyzed via unsupervised cluster analysis, and Lasso logistic regression was employed to assess associations between metabolites and fistula maturation outcomes.

We studied 44 patients (26 males, age 68.0 ± 13.4 years, 34 Caucasians, 21 with diabetes), of whom 28 (63.6%) experienced successful fistula maturation. Metabolomic profiles with 2768 features were correlated with maturation outcomes. Lasso logistic regression identified six metabolites associated with maturation outcomes, with an area under the receiver operating characteristics curve of 0.917 (95% CI: 0.833-1.000). These metabolites are linked to cellular energy production and inflammation, offering new insights into AVF maturation biology. Importantly, our findings remained robust after adjusting for clinical and demographic variables.

Six metabolites identified in plasma samples collected prior to arteriovenous fistula creation were associated with subsequent vascular access maturation outcomes. If validated in larger studies, these biomarkers could aid personalized vascular access planning and inform research into potential novel therapeutic targets.