Under construction: improving arteriovenous fistula maturation

Abstract

Due to a shortage of donor kidneys, patients with end-stage kidney failure often need hemodialysis, a treatment that cleans the blood. To make this possible, surgeons can create an arteriovenous fistula (AVF): a direct connection between an artery and a vein. This high-flow access is the preferred long-term solution, but in up to one-third of patients the AVF does not “mature”: the vein fails to widen and strengthen enough to provide sufficient blood flow for dialysis. Understanding this process is essential to improve patient care and reduce repeated surgeries.

In this thesis, we explored how an AVF matures and why it sometimes fails. Using mouse models, patient samples, and clinical data, we studied how blood vessel cells, signaling molecules such as von Willebrand factor (VWF), and the extracellular matrix that make up blood vessels interact to remodel the vein after surgery. We also examined how specific conditions like polycystic kidney disease affect this process. Together, these studies show that AVF maturation depends on a delicate balance of vessel wall remodelling, inflammation, and molecular signaling. Understanding these mechanisms opens the door to new therapies that could improve AVF success and make dialysis safer and more effective.