Intimal Hyperplasia and Arteriovenous Fistula Failure: Looking Beyond Size Differences

Abstract

The development of venous intimal hyperplasia (IH) has been historically associated with failure of arteriovenous fistulas (AVF) used for hemodialysis. This long-standing assumption, based on histological observations, has been recently challenged by clinical studies indicating that the size of the intima by itself is not enough to explain stenosis or AVF maturation failure. Irrespective of this lack of association, IH is present in most native veins and fistulas, is prominent in many cases, and suggests a role in the vein that may not be reflected by its dimensions. Therefore, the contribution of IH to AVF dysfunction remains controversial. Using only clinical data and avoiding extrapolations from animal models, we critically discuss the biological significance of IH in vein remodeling, vascular access function, and the response of the venous wall to repeated trauma in hemodialysis patients. We address questions and pose new ones such as: What are the factors that contribute to IH in pre-access veins and AVFs? Do cellular phenotypes and composition of the intima influence AVF function? Are there protective roles of the venous intima? This review explores these possibilities, with hopes of rekindling a critical discussion about venous IH that goes beyond thickness and AVF outcomes.

Transcriptomic Analysis Identifies Differentially Expressed Genes Associated with Vascular Cuffing and Chronic Inflammation Mediating Early Thrombosis in Arteriovenous Fistula

“…The creation of AVF is associated with acute inflammation which is necessary for the wound healing and resolution phase but chronicity of inflammation results in thrombosis of the vessels involved in AVF and leads to AVF maturation failure. Thrombosed AVF with chronic inflammation is characterized by increased C-reactive protein (CRP), infiltration of the immune cells including neutrophils and macrophages, increased expression of vascular cell adhesion protein (VCAM)-1, interleukin (IL)-6, and tumor necrosis factor (TNF)-α, neoangiogenesis, neointimal hyperplasia (NIH), and atheromatous plaque formation [ 2 , 3 , 4 , 5 ]. Intimal injury while creating AVF may cause endothelial dysfunction and chronic inflammation leading to AVF maturation failure [ 6 ].…”

Downregulation of the endothelial histone demethylase JMJD3 is associated with neointimal hyperplasia of arteriovenous fistulas in kidney failure

“…The artery injury model is induced by completely removing the endothelial layer and causing a distending mural injury in rat/mice with normal kidney function ( 48 ). In patients with kidney failure, uremic milieu contributes to a multitude of vascular diseases including venous intimal hyperplasia even prior to hemodialysis access surgery ( 7 , 49 , 50 ). Our studies showed that expression level of endothelial JMJD3 in vessel was significantly decreased in the context of chronic renal failure.…”

“…Currently, there remains no effective therapies to prevent AVF maturation failure ( 5 , 6 ), and the mechanisms for fistula loss are still not clearly understood. Neointimal hyperplasia (NIH) is present in most native veins and AVFs, which is prominent in many patients with kidney failure ( 7 ). After AVF creation, expansion of neointima may aggravate inward remodeling leading to the development of stenosis and access failure.…”

Systemic Profile of Cytokines in Arteriovenous Fistula Patients and Their Associations with Maturation Failure

“…Despite the lack of correlation between the plasma levels of all of these factors, they shared potential vascular effects in common such as immune cell infiltration, neovascularization, and platelet aggregation. The role of immune cell infiltration in early AVF remodeling is not clear at the moment (56). However, an exaggerated response to injury may affect the proper healing of the vascular wall.…”