Molecular targets for improving arteriovenous fistula maturation and patency

• Main Authors: Jolanta Gorecka, Arash Fereydooni, Luis Gonzalez, Shin Rong Lee, Shirley Liu, Shun Ono, Jianbiao Xu, Jia Liu, Ryosuke Taniguchi, Yutaka Matsubara, Xixiang Gao, Mingjie Gao, John T Langford, Bogdan Yatsula, Alan Dardik
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2019-01-01
• Series: Vascular Investigation and Therapy
• Subjects: arteriovenous fistula; chronic kidney disease; fistula failure; hemodialysis; maturation
• Online Access: http://www.vitonline.org/article.asp?issn=2589-9686;year=2019;volume=2;issue=2;spage=33;epage=41;aulast=Gorecka

The increasing prevalence of chronic and end-stage renal disease creates an increased need for reliable vascular access; although arteriovenous fistulae (AVF) are the preferred mode of hemodialysis access, 60% fail to mature and only 50% remain patent at 1 year. Fistulae mature by diameter expansion and wall thickening; this outward remodeling of the venous wall in the fistula environment relies on a delicate balance of extracellular matrix remodeling, inflammation, growth factor secretion, and cell adhesion molecule upregulation in the venous wall. AVF failure occurs via two distinct mechanisms with early failure secondary to lack of outward remodeling, that is, insufficient diameter expansion or wall thickening, whereas late failure occurs with excessive wall thickening due to neointimal hyperplasia and insufficient diameter expansion in a previously functional fistula. In recent years, the molecular basis of AVF maturation and failure are becoming understood to develop potential therapeutic targets to aid maturation and prevent access loss. Erythropoietin-producing hepatocellular (Eph) carcinoma receptors, along with their ligands and ephrins, determine vascular identity and are critical for vascular remodeling in the embryo. Manipulation of Eph receptor signaling in adults, as well as downstream pathways, is a potential treatment strategy to improve the rates of AVF maturation and patency. This review examines our current understanding of molecular changes occurring following fistula creation, factors predictive of fistula success, and potential areas of intervention to decrease AVF failure.