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Cellular and molecular mechanisms underlying hemodialysis arteriovenous fistula dysfunction and approaches to promote maturation: a vascular perspective
Journal article   Peer reviewed

Cellular and molecular mechanisms underlying hemodialysis arteriovenous fistula dysfunction and approaches to promote maturation: a vascular perspective

Yan-Ting Shiu, Hannah Northrup, Yufeng Huang, Monique E. Cho and Kanokwan Bunsawat
American journal of physiology. Heart and circulatory physiology, Vol.329(1), pp.H241-H257
07/01/2025
DOI: 10.1152/ajpheart.00010.2025
PMCID: PMC12237592
PMID: 40465509

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Abstract

Hemodialysis requires functional vascular access, which serves as the conduit for blood flow between the patient and the hemodialysis machine. The arteriovenous fistula (AVF), created by surgically connecting an artery to a nearby vein in the upper extremity, is the preferred form of vascular access for maintenance hemodialysis. Newly created AVFs must undergo a maturation process, during which the fistula vein enlarges and develops sufficient lumen size and blood flow to be used effectively for dialysis. However, since the invention of AVFs 60 years ago, rates of AVF maturation failure have remained high. Currently, no proven therapies exist to promote maturation or prevent maturation failure. This review examines the current understanding of the cellular and molecular mechanisms underlying AVF maturation failure, with particular focus on the impact of the chronic kidney disease (CKD) environment on the vascular system. In CKD, patients often have elevated levels of uremic toxins, increased oxidative stress, and chronic inflammation, all of which adversely affect the function of vascular wall cells (such as endothelial cells, vascular smooth muscle cells, and fibroblasts) and circulating cells (such as platelets and immune/inflammatory cells). The goal of this review is to explore the mechanisms influencing both native and AVF vasculature in the context of CKD. In addition, we will discuss current therapies aimed at improving native vasculature in patients with CKD, as well as investigational approaches to promote AVF maturation.
Cardiac & Cardiovascular Systems Cardiovascular System & Cardiology Life Sciences & Biomedicine Peripheral Vascular Disease Physiology Science & Technology

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