Hemodynamics and Vascular Wall Biology Determine Arteriovenous Fistula Maturation

血流动力学和血管壁生物学决定动静脉瘘的成熟

• 批准号: 8278543
• 负责人: Scott A Berceli
• 金额: $ 60.99万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8278543
• 关键词: Ancillary Study; Area; Arteries; Arteriovenous fistula; Attention; Back; Biology; Biomechanics; Blood; Blood Vessels; Blood flow; Caring; Chronic; Clinical; Cohort Studies; Critical Pathways; Data; Data Collection; Data Coordinating Center; Development; Dialysis patients; Dialysis procedure; Enrollment; Failure; Fistula; Forearm; Functional disorder; Hemodialysis; Heterogeneity; Hyperplasia; Innovative Therapy; Investigation; Knowledge; Laboratories; Lead; Left; Length; Link; Liquid substance; Location; Magnetic Resonance Imaging; Mediating; Modeling; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Operative Surgical Procedures; Outcome; Parents; Pathogenesis; Pathway interactions; Patients; Pattern; Physiological Processes; Physiology; Plethysmography; Postoperative Period; Property; Role; Spatial Distribution; Statistical Models; Stenosis; Techniques; Testing; Time; Vascular remodeling; Veins; Venous; brachial artery; experience; hemodynamics; improved; indexing; insight; morphometry; novel; shear stress; time use; usability

DESCRIPTION (provided by applicant): A functional rteriovenous fistula (AVF) is the preferred form of vascular access for chronic hemodialysis. However, up to 60% of AVFs never mature, i.e., achieve sufficient lumen dilation to allow adequate blood flow rate for chronic dialysis. The NIDDK has recently established the Hemodialysis Fistula Maturation (HFM) Consortium to investigate this problem through a 600-patient cohort study at six Clinical Centers, a Data Coordinating Center (DCC) and Core Laboratories. The HFM cohort study will identify predictors of AVF maturation failure, and collect indirect evidence about mechanistic hypotheses. However, its broad scope inevitably limits more direct and extensive investigations of specific mechanisms. We propose an HFM ancillary study, at three HFM Clinical Centers and the DCC, to examine the role of aberrant hemodynamics in the pathogenesis of AVF maturation failure. While alterations in hemodynamic wall shear stress (WSS) are known to modulate vascular remodeling and neointimal hyperplasia formation, the spatial distribution profile of WSS in the developing AVF, and the relationship between this WSS profile and AVF maturation, are currently unclear. In addition, the impact of WSS on the AVF lumen is likely modulated by the pre-existing properties of the vascular wall before AVF creation. Previous studies on WSS in AVF have been small, and have not examined the relationships among WSS, pre-existing vascular wall properties, and AVF outcomes. This ancillary study will collect WSS data in developing AVFs over time using state-of-the art magnetic resonance imaging (MRI) and computational fluid dynamic (CFD) modeling techniques, and link this information with vascular wall property data collected in the parent HFM study. Through this linkage, we will be able to examine the interplay among WSS, vascular wall properties, and AVF maturation over time. In Specific Aim 1, we will enroll 40 patients in each of the three Clinical Centers, for a total of 120 patients, who are already enrolled in the parent HFM cohort study. We will obtain luminal geometry and blood flow data in the AVF by MRI at 2 days, 6 weeks, 6 months and 18 months after AVF creation, and derive WSS profiles from the MRI data using CFD modeling. In Specific Aim 2, we will analyze the relationships between local WSS at 2 days and 6 weeks after AVF creation with subsequent changes in AVF lumen cross-sectional area and blood flow rate at 6 and 18 months. In Specific Aim 3, we will assess whether pre-existing endothelial functionality, venous biomechanics and vein wall morphometry are additional predictors, confounders, or especially modifiers, of the relationships described under Specific Aim 2. Illuminating the interplay of hemodynamics and pre-existing vascular wall properties with the AVF outcomes should lead to novel predictors of AVF maturation, elucidate critical pathways to AVF failure, and point towards innovative therapies supporting successful maturation by targeting these pathways.

描述（由申请人提供）：功能性动静脉瘘（AVF）是慢性血液透析首选的血管通路形式。然而，高达60%的avf从未成熟，即没有达到足够的管腔扩张，以允许足够的血流速率进行慢性透析。NIDDK最近建立了血液透析瘘成熟（HFM）联盟，通过在六个临床中心、一个数据协调中心（DCC）和核心实验室进行的600例患者队列研究来调查这一问题。HFM队列研究将确定AVF成熟衰竭的预测因素，并收集有关机制假设的间接证据。然而，其广泛的范围不可避免地限制了对具体机制的更直接和广泛的研究。我们建议在三个HFM临床中心和DCC进行HFM辅助研究，以检查异常血流动力学在AVF成熟衰竭发病机制中的作用。虽然已知血流动力学壁剪切应力（WSS）的改变可以调节血管重构和新生内膜增生的形成，但目前尚不清楚WSS在AVF发育过程中的空间分布特征，以及这种WSS特征与AVF成熟之间的关系。此外，WSS对AVF管腔的影响可能是由AVF形成前血管壁的已有特性调节的。先前关于AVF中WSS的研究很少，并且没有检查WSS、预先存在的血管壁特性和AVF结局之间的关系。这项辅助研究将利用最先进的磁共振成像（MRI）和计算流体动力学（CFD）建模技术，收集avf发展过程中的WSS数据，并将这些信息与母体HFM研究中收集的血管壁特性数据联系起来。通过这种联系，我们将能够研究WSS、血管壁特性和AVF成熟之间的相互作用。在Specific Aim 1中，我们将在三个临床中心各招募40名患者，总共120名患者，这些患者已经参加了母HFM队列研究。我们将在AVF创建后2天、6周、6个月和18个月通过MRI获得AVF的腔内几何形状和血流数据，并使用CFD建模从MRI数据中获得WSS剖面。在Specific Aim 2中，我们将分析AVF形成后2天和6周的局部WSS与随后6个月和18个月AVF管腔截面积和血流速率的变化之间的关系。在特异性目标3中，我们将评估预先存在的内皮功能、静脉生物力学和静脉壁形态测量是否是特异性目标2中描述的关系的额外预测因素、混杂因素，或者特别是修饰因素。阐明血流动力学和预先存在的血管壁特性与AVF结果的相互作用，将导致AVF成熟的新预测因素，阐明AVF失败的关键途径，并指出通过靶向这些途径支持成功成熟的创新疗法。