Arteriovenous fistulas and arteriovenous grafts are the most commonly used vascular access for hemodialysis in patients with end-stage chronic kidney disease. However, both methods face significant challenges due to the hemodynamic disturbances induced by the arteriovenous anastomosis. This causes changes in vascular structure and blood flow velocity near the anastomosis site after the fistula/graft surgery, and introduces abnormal wall shear stress and cyclic stretch. This leads to endothelial cell dysfunction, vascular smooth muscle cell proliferation, and adverse remodeling. The resulting effects include low patency rates due to vascular stenosis caused by intimal hyperplasia and insufficient outward remodeling. Additionally, the high flow conduit has been linked to adverse cardiac remodeling. To address this, various strategies have been explored to correct these localized hemodynamic abnormalities, aiming to improve long-term patency rates. In this review, an overview is provided of the current surgical techniques, anastomosis types, anastomosis angles, external scaffolds, modified fistula designs, and types of grafts. It evaluates the impact of these approaches on local hemodynamics in the access conduit and their potential effects on patient outcomes.

Disturbed flow is one of the pathological initiators of endothelial dysfunction in intimal hyperplasia (IH) which is commonly seen in vascular bypass grafts, and arteriovenous fistulas. Various in vitro disease models have been designed to simulate the hemodynamic conditions found in the vasculature. Nonetheless, prior investigations have encountered challenges in establishing a robust disturbed flow model, primarily attributed to the complex bifurcated geometries and distinctive flow dynamics. In the present study, we aim to address this gap by introducing an in vitro bypass flow model capable of inducing disturbed flow and other hemodynamics patterns through a pulsatile flow in the same model. To assess the model's validity, we employed computational fluid dynamics (CFD) to simulate hemodynamics and compared the morphology and functions of human umbilical venous endothelial cells (HUVECs) under disturbed flow conditions to those in physiological flow or stagnant conditions. CFD analysis revealed the generation of disturbed flow within the model, pinpointing the specific location in the channel where the effects of disturbed flow were observed. High-content screening, a single-cell morphological profile assessment, demonstrated that HUVECs in the disturbed flow area exhibited random orientation, and morphological features were significantly distinct compared to cells in the physiological flow or stagnant condition after a two days of flow exposure. Furthermore, HUVECs exposed to disturbed flow underwent extensive remodeling of the adherens junctions and expressed higher levels of endothelial cell activation markers compared to other hemodynamic conditions. In conclusion, our in vitro bypass flow model provides a robust platform for investigating the associations between disturbed flow pattern and vascular diseases.