Fibrotic Venous Remodeling and Nonmaturation of Arteriovenous Fistulas

Abstract

The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR], 1.55; 95% confidence interval [95% CI], 1.05 to 2.30; =0.03, per 10% absolute increase in fibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population's median value (OR, 2.63; 95% CI, 1.07 to 6.46;=0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95% CI, 1.03 to 1.84; =0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.

PDGFRA in vascular adventitial MSCs promotes neointima formation in arteriovenous fistula in chronic kidney disease

“…Fibrogenic vein and artery limit AVF outward expansion and induces inward remodeling. A recent report showed that collagen deposition in the vein is associated with AVF failure in patients with ESRD (25). Second, activation of PDGFRA in GMCs induces GMC differentiation into myofibroblasts or VSMCs, directly contributing to CKD-induced neointima formation.…”

Mineralocorticoid receptor: A hidden culprit for hemodialysis vascular access dysfunction

“…In support of this, more than 70% of pre-access veins in ESRD patients have significant hyperplasia at the time of surgery [15]. However, recent studies demonstrated that the contribution of pre-existing IH to AVF nonmaturation is likely very limited, as shown by Martinez et al [4] and also by the Hemodialysis Fistula Maturation (HFM) Group [16], which is the largest multicenter prospective study of AVF with standardized training for data collection and ultrasound measurements and uniform criteria for defining stenosis. As for post-operative hyperplasia, its role in AVF non-maturation and failure has been less studied.…”

“…As for post-operative hyperplasia, its role in AVF non-maturation and failure has been less studied. However, more and more evidence suggests that the effects of IH on AVF non-maturation seem to have been overestimated [4,17,18]. To date, it remains uncertain and controversial if post-operative IH is a causative factor for AVF failure and if post-operative intimal hyperplasia is a primary cause or simply a worsening factor for AVF failure.…”

“…Vascular access dysfunction is associated with over activation of α-smooth muscle actin (α-SMA) positive cells, like myofibroblasts and vascular smooth muscle cells (VSMC). Both cell types proliferate and migrate from adventitia or media to intima under the local influence of diverse cytokines, culminating in excess extracellular matrix (ECM) deposition, IH, vascular fibrosis and AVF failure [4]. However, to date, there are still no effective interventional measures to prevent vascular fibrosis or IH and improve the patency of vascular access.…”

Effects of cardiovascular medications on primary patency of hemodialysis arteriovenous fistula

“…The findings of these studies suggested that neointimal hyperplasia itself does not directly contribute to AVF failure. On the other hand, Vazquez-Padron's group showed that inflammation of vascular smooth muscle cells and increased postoperative medial fibrosis are the main mechanism of poor AVF outward remodeling, which in turn leads to AVF stenosis and failure 28,29 . Based on the result of these studies, thrombosis is more likely a result of AVF stenosis rather than the inciting event of AVF failure.…”