Abstract

Introduction: Local adipose biomarkers have recently been shown to correlate with outward remodeling (adiponectin, IL-8, MCP-1, resistin and TNF) and flow volume (adiponectin, MCP-1) after human hemodialysis AVF creation. As a potential mechanism underlying this observation, we hypothesized that vascular anatomy and physiologic function is dependent on local adipose phenotype. Methods: During AVF creation surgery, adipose tissue contiguous to the proximal anastomosis was obtained from patients at two institutions participating in the NIDDK Hemodialysis Fistula Maturation (HFM) Study (n=112). Nine adipose-associated biologic mediators (adiponectin, IL-1 beta, IL-6, IL-8, leptin, MCP-1, PAI-1, resistin, and TNF) were quantified. Levels of adipose biomarkers were correlated to measurements obtained from comprehensive pre-operative non-invasive vascular anatomic and functional studies performed as part of the HFM Study protocol using Spearman correlation (before logarithmic transformation) and Pearson correlation (after transformation). Bonferroni correction was performed for multiple testing (alpha/9=0.006) Results: Smaller brachial arterial diameter correlated with higher IL-8 (r=-0.23, 95% CI -0.41 to -0.03, p=0.02), MCP-1 (r=-0.24, 95% CI -0.42 to -0.05, p=0.01), and PAI-1 (r=-0.25, 95% CI -0.42 to -0.05, p=0.01) levels and lower brachial arterial flow velocity correlated with higher MCP-1 (r=-0.22, 95% CI -0.40 to -0.02, p =0.03), but the associations were not significant after Bonferroni adjustment. Brachial artery flow- and nitroglycerin-mediated dilation (FMD and NMD), carotid-radial and -femoral pulse wave velocity (PWV), augmentation index, and the slope of the venous volume-pressure relationship did not correlate with adipose mediator levels. Conclusions: While there was suggestion of a relationship between local adipose mediator levels and baseline brachial artery characteristics, relationships with vascular function as assessed by FMD, NMD, PWV and venous capacitance slope were not evident using tests of monotonic associations. Processes not reflected in these measures of vascular characteristics and function may underlie relationships between adipose phenotype and vascular remodeling in human AVFs.

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