Sterile inflammation in the pathogenesis of maturation failure of arteriovenous fistula.

Abstract

Chronic kidney disease is a widespread terminal illness that afflicts millions of people across the world. Hemodialysis is the predominant therapeutic management strategy for kidney failure and involves the external filtration of metabolic waste within the circulation. This process requires an arteriovenous fistula (AVF) for vascular access. However, AVF maturation failures are significant obstacles in establishing long-term vascular access for hemodialysis. Appropriate stimulation, activation, and proliferation of smooth muscle cells, proper endothelial cell orientation, adequate structural changes in the ECM, and the release of anti-inflammatory markers are associated with maturation. AVFs often fail to mature due to inadequate tissue repair and remodeling, leading to neointimal hyperplasia lesions. The transdifferentiation of myofibroblasts and sterile inflammation are possibly involved in AVF maturation failures; however, limited data is available in this regard. The present article critically reviews the interplay of various damage-associated molecular patterns (DAMPs) and the downstream sterile inflammatory signaling with a focus on the NLRP3 inflammasome. Improved knowledge concerning AVF maturation pathways can be unveiled by investigating the novel DAMPs and the mediators of sterile inflammation in vascular remodeling that would open improved therapeutic opportunities in the management of AVF maturation failures and its associated complications.