title: Hemodynamic Shear Stress and Endothelial Dysfunction in Hemodialysis Access.
abstract: Surgically-created blood conduits used for chronic hemodialysis, including native arteriovenous fistulas (AVFs) and synthetic AV grafts (AVGs), are the lifeline for kidney failure patients. Unfortunately, each has its own limitations: AVFs often fail to mature to become useful for dialysis and AVGs often fail due to stenosis as a result of neointimal hyperplasia, which preferentially forms at the graft-venous anastomosis. No clinical therapies are currently available to significantly promote AVF maturation or prevent neointimal hyperplasia in AVGs. Central to devising strategies to solve these problems is a complete mechanistic understanding of the pathophysiological processes. The pathology of arteriovenous access problems is likely multi-factorial. This review focuses on the roles of fluid-wall shear stress (WSS) and endothelial cells (ECs). In arteriovenous access, shunting of arterial blood flow directly into the vein drastically alters the hemodynamics in the vein. These hemodynamic changes are likely major contributors to non-maturation of an AVF vein and/or formation of neointimal hyperplasia at the venous anastomosis of an AVG. ECs separate blood from other vascular wall cells and also influence the phenotype of these other cells. In arteriovenous access, the responses of ECs to aberrant WSS may subsequently lead to AVF non-maturation and/or AVG stenosis. This review provides an overview of the methods for characterizing blood flow and calculating WSS in arteriovenous access and discusses EC responses to arteriovenous hemodynamics. This review also discusses the role of WSS in the pathology of arteriovenous access, as well as confounding factors that modulate the impact of WSS.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Fitts
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Pike
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Kasey
authors.initials: K
authors.lastname: Anderson
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Shiu
keywords: Arteriovenous fistula; Arteriovenous grafts; Endothelial cells; Hemodialysis vascular access; Hemodynamics; Shear stress