Local Adipose-Associated Mediators and Adaptations Following Arteriovenous Fistula Creation

Abstract

Introduction: Local inflammation is an important regulator of vascular remodeling. We hypothesized that adipose tissue adjacent to hemodialysis arteriovenous fistulae modulates maturation.

Methods: During fistula creation, perivenous adipose was collected from 111 participants in the Hemodialysis Fistula Maturation Study. Nine adipose-associated mediators were measured. Duplex ultrasound was performed at 4 time points postoperatively from 1 day to first cannulation (10-26 weeks). Associations between logarithmically transformed biomarker levels and fistula remodeling were evaluated using mixed effects regression.

Results: Elevated interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 were associated with a reduction in the fractional vein diameter during the early time frame of 1 day to 2 weeks (diameter change of 26.6% and 20.4% at the 25th and 75th percentile for IL-6, P = 0.01; 27.8% and 21.1% at the 25th and 75th percentile for MCP-1, P = 0.02), but not in later stages of remodeling. Local leptin levels showed a significant negative correlation with fractional venous flow increase between 2 and 6 weeks (percent flow change 31.4% and 11.3% at the 25th and 75th percentile for leptin, P = 0.03).

Conclusion: Thus, impaired fistula vein dilation and reduced capacity for flow augmentation associate with specific local adipose phenotypic signatures in a time-dependent manner. In view of adipose tissue plasticity, these findings raise the possibility of novel adipose-based strategies to facilitate fistula maturation.

Keywords: chronic kidney disease; fistula maturation; hemodialysis; inflammation; perivascular adipose tissue.

Figure 1

Fractional AVF diameter change as a function of local adipose mediator levels during each time interval. A significant relationship between the fractional change in diameter and both IL-6 (P = 0.01) and MCP-1 (P = 0.02) was observed during the early phase of fistula maturation. This corresponded to a 7.9% and 12.6% decrease in fistula diameter for every 10 pg IL-6/mg tissue or 10 pg MCP-1/mg tissue increase in IL-6 and MCP-1 levels, respectively. In terms of absolute vein diameter changes, this represented a 0.45-mm and 0.30-mm difference between the 10th and 90th percentiles of IL-6 and MCP-1 concentrations, respectively. AVF, arteriovenous fistula; IL, interleukin; MCP, monocyte chemoattractant protein.

Figure 2

Fractional AVF flow change as a function of local adipose leptin levels during each time interval. A significant relationship between the fractional change in flow and leptin (P = 0.01) was observed during the intermediate phase of fistula maturation. This corresponded to a 26.8% decrease in flow for every 10-pg leptin/mg tissue increase in leptin levels. In terms of absolute flow changes, this represented a 132-ml/min difference between the 10th and 90th percentiles of leptin concentration.