Arteriovenous fistulas (AVF) are the preferred vascular access for hemodialysis, however patency rates remain low. Animal AVF models are essential for uncovering mechanisms of AVF remodeling. Yet most lack coexisting chronic kidney disease (CKD), critical to AVF failure. Existing CKD-AVF models are often acute surgical models and cause substantial discomfort and high mortality, limiting their translational value. This study assessed high-oxalate diet-induced kidney injury in a mouse AVF model and its effect on AVF remodeling. Male and female C57BL/6 J mice were fed either a high-oxalate or control diet for six weeks. AVF surgery was performed at week three. Kidney function (glomerular filtration rate GFR, plasma urea), blood pressure, and ultrasound-assessed AVF volume were monitored. Three weeks post-surgery, AVFs, blood, and kidneys were analyzed by immunohistochemistry and flow-cytometry to assess morphometry, endothelial damage, inflammation, and immune activation. High-oxalate diet reduced GFR by 49% ( P < 0.001) and increased plasma urea, confirming kidney injury. AVF volume did not differ between groups, whereas mean arterial pressure was 23% higher in the high-oxalate group ( P = 0.024). AVFs from these mice showed 13% less outward remodeling ( P = 0.026), increased endothelial damage, immune cell infiltration and vascular calcification. Flow-cytometry demonstrated increased systemic immune activation in the high-oxalate group. The high-oxalate-induced chronic kidney injury-AVF model express key similarities to human impaired AVF remodeling, including long-term kidney failure, hypertension, endothelial damage and immune activation. By reducing animal burden and improving disease representation, this model advances preclinical AVF research towards greater translational applicability. • Arteriovenous fistulas have low patency and preclinical research models are needed to develop therapeutic interventions. • Current AVF mouse models lack key characteristics of chronic kidney disease • High-oxalate diet-induced kidney injury provides a physiologically representative mouse model for preclinical AVF research. • High-oxalate diet-induced kidney injury results in increased endothelial damage and immune activation and alters AVF remodeling.
Winter et al. (Sun,) studied this question.