Adipose phenotype predicts early human autogenous arteriovenous hemodialysis remodeling

Abstract

Objective Substantial proportions of autogenous arteriovenous hemodialysis access fistulas (AVF) 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 juxtaposed to the developing AVF associate with subsequent inward or outward vein wall remodeling. Methods Clinical data and subcutaneous adipose tissue were collected from consented patients undergoing AVF creation (n=22). Tissue was assayed (protein levels) for IL-6, IL-8, leptin, TNF-α, MCP-1, resistin, and adiponectin. Duplex ultrasound vein dimensions were acquired pre-operatively and 4–6 weeks post-operatively at a point 1cm cephalad to the arteriovenous anastomosis (most common location of AVF stenosis). Results The vein at the assayed location outwardly remodeled 55.7% on average (pre-median 3.7 mm, post-median 4.7 mm; p=0.005). Pre-operative vein diameter failed to correlate with post-operative size at the point of assay (R=0.31, p=0.155) unless two outliers were excluded (R=0.64, p=0.002). After removal of the same outliers, the correlation coefficient between venous diameter change (pre-operative vs. post-operative) and IL-8, TNF-α, MCP-1, resistin, and adiponectin was −0.49, −0.79, −0.66, −0.64, and −0.69 respectively (p<0.05). Post-operative AVF flow volume correlated with MCP-1 (−0.53, p<0.05) and adiponectin (−0.47, p<0.05). Conclusion 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 pre-operative 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.

Inflammation in Vein Graft Disease

“…PVAT harbors numerous amounts of inflammatory cells. Damage to PVAT results in an inflammatory response driven by adipocyte-derived factors such as resistin, leptin, or the cytokines IL-6, TNF-α, and CCL2 ( 154 ). Protective effects of adiponectin on NADPH oxidase, superoxide production and NO bioavailability in the vessel wall are reduced after PVAT damage ( 155 ).…”

Local Adipose-Associated Mediators and Adaptations Following Arteriovenous Fistula Creation

“…We reported that levels of local adipose-associated mediators correlated with markers of vein remodeling at a single time point 4 to 6 weeks after access surgery. 25 Here we expanded on that work by evaluating vascular wall adaptations at several time points, which extended from placement to first cannulation, and in a larger, more diverse, and better-described patient population.…”

“… 22 , 23 , 24 Recently, we demonstrated in a small prospective study that levels of adipose interleukin (IL)-8, tumor necrosis factor-α, monocyte chemoattractant protein (MCP)-1, resistin, and adiponectin were inversely correlated with venous diameter change, and MCP-1 and adiponectin were inversely correlated with flow volume in human AVF at 4 to 6 weeks after access creation. 25 …”

Local perivascular adiponectin associates with lower extremity vascular operative wound complications

“…42 We also recently demonstrated that local adipose adiponectin was inversely correlated with eventual flow volume (a marker of arteriovenous fistula maturation) in the early stages following hemodialysis access creation surgery. 43 Investigators studying circulating plasma adipocytokine levels found a nearly significant trend toward elevated preoperative leptin in patients who developed SSI. 17, 18 A similar correlation between circulating adiponectin and wound infection was not found.…”