Arteriovenous access failure: more than just intimal hyperplasia?

Abstract

Haemodialysis vascular access patency is severely compromised by fistula non-maturation and access stenosis. Intimal hyperplasia (IH) is considered the culprit lesion in failed fistulas, resulting in luminal narrowing and stenosis. This review focuses on the biology and pathophysiology of fistula failure and highlights not only the classically associated IH but also some relatively neglected but potentially important contributors such as inadequate outward remodelling. In addition, the complex process and fragile balance of successful fistula maturation might be partially hindered by pre-existent chronic kidney disease-mediated vasculopathy. Further unravelling the (patho)physiology of outward remodelling and IH could contribute to novel therapies and enhance fistula patency.

The mouse aortocaval fistula recapitulates human arteriovenous fistula maturation

“…Despite the superiority of AVF access compared with its alternatives, AVFs are still far from perfect. AVFs fail to "mature," e.g., dilate, thicken, and increase flow, before the beginning of dialysis in ϳ20 -50% of cases, with the majority of AVFs requiring some additional therapeutic intervention to mature successfully (9,14,20,21). In addition, 1-yr primary AVF patency rates are typically only 60 -65%, with many mature AVFs subsequently failing secondarily due to neointimal hyperplasia, generally perianastomotic (2,4,7,19,21,22).…”

Challenges in Developing New Therapies for Vascular Access Dysfunction

“…This inability of inward remodeling to entirely explain AVF nonmaturation has underscored the importance of outward remodeling in AVF maturation. Outward remodeling achieves a sustained increase in luminal diameter because of vasodilation and structural vascular enlargement and offsets the luminal encroachment caused by neointimal hyperplasia and inward remodeling; conversely, an AVF with inadequate outward remodeling may not mature even without neointimal hyperplasia (6). Promoting AVF maturation thus requires strategies that not only inhibit inward remodeling but more importantly, promote outward remodeling.…”

Novel Paradigms for Dialysis Vascular Access

“…The histology of AVF nonmaturation has been demonstrated to be secondary to aggressive venous neointimal hyperplasia ( Figure 2, A and B), with the majority of cells within the neointima staining for myofibroblasts, but with contractile smooth muscle cells and fibroblasts also present (6). In addition to aggressive neointimal hyperplasia development, inadequate vasodilation (inward remodeling), resulting in vasoconstriction of the vein, also likely plays an important role in AVF nonmaturation (7)(8)(9)(10).…”