Abstract Background Chronic kidney disease (CKD) affects more than 10% of adults worldwide and is associated with rising mortality and increasing demand for hemodialysis. Hemodialysis requires durable vascular access, with surgically created arteriovenous fistulas (AVFs) being the preferred modality. However, up to 60% of AVFs fail to mature in time for clinical use, whereas others develop excessively high flow that can drive adverse cardiac remodeling and heart failure. These problems reflect incomplete understanding of the biological and biomechanical processes that govern AVF maturation and failure. Aim To summarize the experimental models currently used to study AVF maturation and failure—including animal models, computational approaches and in vitro flow systems—and to compare their respective strengths, limitations and complementary roles in vascular access research. Summary AVF maturation depends on coordinated arterial and venous remodeling in response to abrupt hemodynamic changes after anastomosis. Altered wall shear stress, pressure and cyclic strain activate endothelial and vascular smooth muscle signaling pathways that promote vasodilation, outward remodeling, matrix turnover and wall thickening. When these adaptive responses are blunted or dysregulated, neointimal hyperplasia, stenosis and access failure ensue. These biomechanical stimuli act within a pro-inflammatory, pro-oxidant uremic milieu, in which circulating toxins impair endothelial function, enhance oxidative stress and bias remodeling towards maladaptation. A broad spectrum of experimental platforms has been developed to interrogate these processes: animal models that recapitulate whole-organism physiology, computational models, including computational fluid dynamics and emerging fluid–structure interaction simulations, that resolve local hemodynamics and wall mechanics; conventional in vitro systems for controlled mechanobiology studies; and emerging microfluidic and macrofluidic devices that impose defined shear waveforms in physiologically relevant geometries. Each model captures selected spatial, temporal or biochemical dimensions of AVF biology, but each is constrained by trade-offs in scalability, fidelity, throughput or translational relevance. Conclusion AVF maturation and failure arise from tightly coupled biomechanical and biological interactions, shaped by hemodynamic forces and uremia-related vascular dysfunction. No single experimental platform can encompass this complexity. Progress will depend on systematic comparison of available models and their deliberate integration into a coherent multimodal framework, in which insights from animal studies, computational simulations and in vitro flow systems are used in a complementary manner. Such an approach is essential to identify predictive biomarkers, clarify mechanisms of maladaptive remodeling and guide the rational design of targeted interventions to improve AVF patency and clinical outcomes.
Shah et al. (Thu,) studied this question.