Modulation of the Hemodynamic Factors Associated with AVF Maturation

描述（由申请人提供）： 增加动静脉内瘘（AVF）使用的国家举措产生了增加AVF未成熟（约30%）和导管使用率（27%）的非预期后果。已经确定了多种因素导致AVF不成熟。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，它们不足以单独预测成功的成熟。由AVF引起的流速增加导致剪切应力增加，剪切应力作为动脉和流出静脉扩张的刺激。剪应力调节AVF成熟的机制尚不清楚。总体假设-剪切应力（由局部和全身环境调节）可预测AVF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/不成熟的因素。方法：制定方案以确定与AVF成熟/不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AVF成熟/不成熟的贡献。方法：在使用超声创建AVF之前，将确定肱动脉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对AVF成熟/不成熟的影响。方法：将在整个围手术期测量CRP、IL-6、MCP-1、slCAM-1和循环内皮细胞的血浆水平。具体目标4：确定剪切应力和局部/全身环境对成熟/不成熟的关键相互作用。方法：在整个围手术期，将使用高分辨率超声对AVF吻合口近端的流入动脉和流出静脉进行成像。将评估直径和速度变化，并计算AVF流量和剪切应力。该方案将确定导致动静脉瘘成功开发的因素，动静脉瘘是用于将患者连接到血液透析机的扩大血管。这将显著改善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.