Background: Arteriovenous fistula (AVF) stenosis remains an important cause of AVF maturation failure, for which there are currently no effective therapies. We examined the pattern and phenotype of cellular proliferation at different timepoints in a mouse model characterized by a peri-anastomotic AVF stenosis. Methods: Standard immunohistochemical analyses for cellular proliferation and macrophage infiltration were performed at 2, 7 and 14 d on our validated mouse model of AVF stenosis to study the temporal profile, geographical location and cellular phenotype of proliferating and infiltrating cells in this model. Results: Adventitial proliferation and macrophage infiltration (into the adventitia) began at 2 d, peaked at 7 d and then declined over time. Surprisingly, there was minimal macrophage infiltration or proliferation in the neointimal region at either 7 or 14 d, although endothelial cell proliferation increased rapidly between 2 d and 7 d, and peaked at 14 d. Conclusions: Early and rapid macrophage infiltration and cellular proliferation within the adventitia could play an important role in the downstream pathways of both neointimal hyperplasia and inward or outward remodelling.

The arteriovenous fistula (AVF) is the preferred method of vascular access for hemodialysis; however, 30–50% of AVFs undergo primary maturation failure and are unsuitable for clinical use. As disturbed hemodynamics initiate endothelial injury and intimal hyperplasia, we designed an endovascular flow-conditioning anastomotic device (FCAD) to directly improve AVF hemodynamics and protect the anastomotic region. Using computational fluid dynamics, we characterized the flow field and wall shear stress (WSS) profiles in idealized AVF models with and without the FCAD. Incorporation of the FCAD into a brachiocephalic AVF model reduced regions of oscillatory WSS and generated a symmetrical flow profile in the draining vein compared to a reference AVF. Parametric studies identified an FCAD geometry with a tab angle, height, and aspect ratio of 30°, 0.1 diameters, and 1.0 that increased time-averaged WSS along the inner venous wall and achieved a physiological WSS (1–3 Pa) without inducing regions of oscillatory flow throughout the cardiac cycle. Similar findings were observed with an in vitro model using particle image velocimetry. This study demonstrates the feasibility of the FCAD to normalize venous flow and WSS while imposing minimal resistance to blood flow. Restoring physiological WSS levels on the venous wall may help preserve endothelial function and improve AVF maturation.