Abstract
As of 2023, approximately 800,000 people suffer from End Stage Renal Disease (ESRD) in the United States, with nearly 70% relying on hemodialysis through a vascular access as their renal replacement therapy. The preferred way to establish vascular access is through an arteriovenous fistula (AVF), which are surgically created by anastomosing a vein to a nearby artery. When the vein is connected to the arterial circulation, it is exposed to supraphysiological flow rates (more than 20x the normal venous flow), wall shear stress, and an increased oxidative load. The venous adaptation to these conditions, known as venous remodeling, results in a thicker wall and larger luminal diameter. However, the molecular mechanisms behind this remarkable adaptation remain unclear. After surgical creation, the AVF has two possible outcomes; 1) AVF failure, defined by flow rates below 600mL/min, and a diameter of less than 6mm or 2) AVF maturation which means flow rates above 600mL/min, larger diameter and functioning as a suitable conduit for repeated vascular access. Unfortunately, 40-50% of all AVFs fail to become viable for hemodialysis without an intervention, exposing an already vulnerable patient population to additional surgical procedures and limiting their access to lifesaving hemodialysis sessions. AVF failure is associated with stenosis or narrowing of the venous lumen which is secondary to medial fibrosis of the vein and neointimal hyperplasia.