Abstract 275: The Journey of the Basilic Vein After Arteriovenous Anastomosis: The Transcriptomic Landscape of Hemodialysis Fistulas with Distinct Maturation Outcomes

The hemodialysis fistula is surgically created by anastomosing a vein to an artery and allowing this vein to remodel (mature) into a larger vessel that is suitable for cannulation. Unfortunately, up to 50% of arteriovenous fistulas (AVFs) fail to mature, generating stenotic segments that compromise blood flow and increase the risk of life-threatening complications. The biological mechanisms underlying AVF maturation or failure remain uncertain. In this case-control study, we applied whole transcriptome RNA sequencing to study the transformation of the basilic vein after AVF creation, in association with maturation outcomes. Paired venous samples ( i.e. , pre-access veins and the resulting fistulas) were obtained from 17 patients who underwent two-stage AVF creation (10 matured and 7 failed). All AVFs were collected within 74 ± 31 days (mean ± SD) after arteriovenous anastomosis (first-stage surgery). Over 9,500 genes were differentially expressed between veins and AVFs using pairwise transcriptomic analyses (FDR<0.05). When analyzed by outcome, 8,529 were differentially expressed between veins and AVFs that matured, whereas 3,807 were statistically different in paired tissues that failed. These numbers reflect the drastic vascular transformation that occurs after AVF creation, a transformation that is more extensive when vein maturation proceeds successfully. The large transcriptional differences between AVFs and veins from the same individuals also suggest global changes in chromatin remodeling and cellular phenotypic composition. The RNA expression of 44 genes changed significantly (>2 folds) between AVFs and veins specifically in the failure subgroup. These included ECM proteins ( COL25A1, TNR ), endothelial cell markers ( EMCN , PLVAP ), mediators of vesicular transport ( CPLX1, SYT16 ), and genes involved in vascular reactivity and hemostasis ( ACE , HTR1F , PTGDS ). These analyses illustrate for the first time the transcriptomic landscape of pre-access basilic veins as they transform into functioning or non-functioning fistulas. Importantly, this study provides the basis for the identification of molecular pathways that underlie maturation or failure of hemodialysis fistulas.