Modulation of the Hemodynamic Factors Associated with AVF Maturation

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The national initiatives to increase the use of arteriovenous fistulas (AVF) have had the unintended consequences of increasing the AVF non-maturation (approximately 30%)and catheter usage rates (27%). Multiple factors have been identified to contribute to the non-maturation of AVFs. The quality of the inflow artery and the outflow vein are likely foremost among these factors, however, they are not sufficient alone to predict successful maturation. The increased flow velocity that results from the AVF leads an increase of shear stress that serves as stimulus for both the artery and outflow vein to dilate. The mechanism by which shear stress modulates AVF maturation remains unknown. Overall Hypothesis - Shear stress, as modulated by the local and systemic milieu, predicts maturation/non- maturation of the AVF. Specific aim 1: Determine the factors that predict AVF maturation/non-maturation in cooperation with the other centers in the consortium. Approach: Develop a protocol to identify the specific factors associated with AVF maturation/non-maturation and their underlying mechanisms. Specific aim 2: Determine the contribution of the baseline characteristics of the artery to AVF maturation/non-maturation. Approach: Brachial artery distensibility and flow mediated dilation (endothelial-dependent) will be determined prior to the creation of the AVF using ultrasound. Specific aim 3: Determine the contribution of the systemic inflammatory response and endothelial cell dysfunction on AVF maturation/non-maturation. Approach: The plasma levels CRP, IL-6,MCP-1, slCAM-1, and circulating endothelial cells will be measured throughout the perioperative period. Specific aim 4: Determine the critical interplay between shear stress and the local/systemic milieu on maturation/non-maturation. Approach: The inflow artery proximal to the AVF anastomosis and the outflow vein will be imaged with high-resolution ultrasound throughout the perioperative period. Diameter and velocity changes will be assessed and both AVF flow and shear stress calculated. The protocol will identify the factors that lead to successful development of arteriovenous fistulas, the enlarged blood vessels used to connect patients to the hemodialysis machine. This will significantly improve the overall quality of life for patients on dialysis.