Modulation of the Hemodynamic Factors Associated with AVF Maturation

描述(由申请人提供)： 增加动静脉瘘(AVF)使用率的国家倡议产生了意想不到的后果，增加了AVF未成熟(约30%)和导管使用率(27%)。动静脉曲张未成熟的原因是多方面的。在这些因素中，流入动脉和流出静脉的质量可能是最重要的，然而，它们本身并不足以预测是否成功成熟。AVF导致的血流速度增加导致切应力增加，这是动脉和流出静脉扩张的刺激因素。目前尚不清楚切应力调节AVF成熟的机制。总体而言，受局部和全身环境调节的剪应力预示着动静脉动静脉瘘的成熟/不成熟。具体目标1：与联盟中的其他中心合作，确定预测AVF成熟/未成熟的因素。方法：制定一项方案，以确定与AVF成熟/未成熟相关的特定因素及其潜在机制。具体目标2：确定动脉的基线特征对动静脉瘘成熟/未成熟的贡献。方法：在使用超声创建动静脉动静脉瘘之前，将确定肱动脉的扩张性和血流介导的扩张(内皮依赖性)。具体目标3：确定全身炎症反应和内皮细胞功能障碍在AVF成熟/未成熟中的作用。方法：测定围术期血浆CRP、IL-6、MCP-1、sLCAM-1和循环内皮细胞的水平。具体目标4：确定切应力和局部/全身环境对成熟/未成熟的临界相互作用。方法：动静脉瘘吻合口近端的流入动脉和流出静脉将在整个围手术期用高分辨率超声成像。将评估直径和速度的变化，并计算AVF流动和剪应力。该方案将确定导致动静脉瘘成功发展的因素，动静脉瘘是用来连接患者和血液透析机的扩大的血管。这将显著提高透析患者的整体生活质量。

DESCRIPTION (provided by applicant): 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.