"Venopathy" at work: recasting neointimal hyperplasia in a new light

Abstract

Hemodialysis vascular access is a unique form of vascular anastomosis. Although it is created in a unique disease state, it has much to offer in terms of insights into venous endothelial and anastomotic biology. The development of neointimal hyperplasia (NH) has been identified as a pathologic entity, decreasing the lifespan and effectiveness of hemodialysis vascular access. Subtle hints and new data suggest a contrary idea-that NH, to some extent an expected response, if controlled properly, may play a beneficial role in the promotion of maturation to a functional access. This review attempts to recast our understanding of NH and redefine research goals for an evolving discipline that focuses on a life-sustaining connection between an artery and vein.

Figure 1

Neointimal hyperplastic lesions of various degrees in a porcine model of AVF. A: Mild NH; B: Moderate NH; C: Severe NH with luminal compromise

Figure 2

Neointimal hyperplasia of vascular access can develop and progress through several pathways. A: Normal vein prior to access creation; B: No vascular remodeling after access creation; C: Luminal narrowing (NH) resulting in luminal compromise due to smooth muscle proliferation and inflammation; D: outward dilatation (maturation) resulting in luminal preservation of the AVF.

Figure 3

Neointimal hyperplasia in the lumen of an AVG (A), in the lumen of a stent (B), and in native vein (C) are traditionally regarded as the same pathologic process, but little is currently known about the genetic, cellular, and inflammatory differences in the three types of lesions.

Figure 4

Broad translational investigative efforts can begin to unravel the complex interplay of NH and its pathologic origins and therapeutic targets (arrows can be understood as “processes leading to understanding of other processes” in this diagram. Note: arrows may become bidirectional as our understanding of NH develops).

Figure 5

IVUS imaging of AVF lesions. Mild (A), moderate (B), and severe (C) NH lesions. White circle – lumen of AVF. Black arrow – NH. Dark circle – ultrasound transducer. Note that ultrasound transducer occludes the lumen of the AVF in the severe lesion (C).