Background: Arteriovenous fistulae (AVF) are the preferred access for hemodialysis but still have poor rates of maturation and patency limiting their clinical use. The underlying mechanisms of venous remodeling remain poorly understood, and only limited numbers of unbiased approaches have been reported.
Methods: Biological Gene Ontology (GO) term enrichment analysis and differentially expressed genes (DEG) analysis were performed for three AVF datasets. A microRNA enrichment analysis and L1000CDS2 query were performed to identify factors predicting AVF patency.
Results: The inflammatory and immune responses were activated during both early and late phases of AVF maturation, with upregulation of neutrophil and leukocyte regulation, cytokine production, and cytokine-mediated signaling. In men with failed AVF, negative regulation of myeloid-leukocyte differentiation and regulation of macrophage activation were significantly upregulated. Compared to non-diabetic patients, diabetic patients had significantly reduced immune response-related enrichment such as cell activation in immune response, regulation of immune-effector process, and positive regulation of defense response; in addition, diabetic patients showed no enrichment of the immune response-regulating signaling pathway.
Conclusions: These data show coordinated, and differential regulation of genes associated with AVF maturation, and different patterns of several pathways are associated with sex differences in AVF failure. Inflammatory and immune responses are activated during AVF maturation and diabetes may impair AVF maturation by altering these responses. These findings suggest several novel molecular targets to improve sex specific AVF maturation.
Keywords: Arteriovenous fistulae; GO for biological processes; diabetes; inflammation; sex difference.