Adipose phenotype predicts early human autogenous arteriovenous hemodialysis remodeling

Abstract

Objective: Substantial proportions of autogenous arteriovenous fistulas (AVFs) for hemodialysis access fail to mature for unclear reasons. AVFs develop in a large mass of surrounding adipose tissue that is increasingly recognized as an active participant in the vascular response to injury via paracrine and endocrine mechanisms. We thus hypothesized that baseline phenotypic characteristics of the adipose tissue juxtaposed to the developing AVF associate with subsequent inward or outward vein wall remodeling.

Methods: Clinical data and subcutaneous adipose tissue were collected from 22 consented patients undergoing AVF creation. Tissue was assayed (protein levels) for interleukin (IL)-6, IL-8, leptin, tumor necrosis factor-α, monocyte chemoattractant protein-1 (MCP-1), resistin, and adiponectin. Vein dimensions were acquired by duplex ultrasound imaging, preoperatively and at 4 to 6 weeks postoperatively, 1 cm cephalad to the arteriovenous anastomosis, which is the most common location of AVF stenosis).

Results: The vein at the assayed location outwardly remodeled 55.7% on average (median before, 3.7 mm; median after, 4.7 mm; P = .005). The preoperative vein diameter failed to correlate with postoperative size at the point of assay (R = 0.31; P = .155) unless two outliers were excluded (R = 0.64; P = .002). After removal of the same outliers, the correlation coefficient between venous diameter change (preoperative vs postoperative) and IL-8, tumor necrosis factor-α, MCP-1, resistin, and adiponectin was -0.49, -0.79, -0.66, -0.64, and -0.69, respectively (P < .05). Postoperative AVF flow volume correlated with MCP-1 (R = -0.53; P < .05) and adiponectin (R = -0.47; P < .05).

Conclusions: These data reveal a novel relationship between local adipose phenotype and the eventual venous wall response to hemodynamic perturbation in humans. The predictive value of these mediators generally equaled or exceeded that of preoperative vein size. Beyond providing mechanistic insights into vascular wall adaptations due to flow perturbations, this discovery suggests that strategies focused on altering adipose tissue biology may improve AVF maturation.