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）：功能性旋转瘘（AVF）是慢性血液透析的首选血管访问形式。但是，多达60％的AVF永远不会成熟，即实现足够的管腔扩张，以使慢性透析的足够血流量。 NIDDK最近通过在六个临床中心，数据协调中心（DCC）和核心实验室的600名患者队列研究来研究了血液透析瘘成熟（HFM）联盟。 HFM队列研究将确定AVF成熟失败的预测指标，并收集有关机械假设的间接证据。但是，其广泛的范围不可避免地限制了对特定机制的更直接和广泛的研究。我们在三个HFM临床中心和DCC上提出了一项HFM辅助研究，以检查异常血液动力学在AVF成熟衰竭发病机理中的作用。尽管已知血液动力学壁剪应力（WSS）的改变会调节血管重塑和新内膜增生形成，但WSS在发育中的AVF中的空间分布分布以及此WSS谱和AVF成熟之间的关系尚不清楚。此外，WSS对AVF管腔的影响可能会受到AVF创建之前血管壁的先前特性的调节。先前对AVF中WSS的研究很小，并且没有检查WSS之间的关系，预先存在的血管壁特性和AVF结果。这项辅助研究将使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WSS数据，以开发AVF，并将这些信息与亲本HFM研究中收集的血管壁属性数据联系起来。通过这种联系，我们将能够随着时间的流逝研究WSS，血管壁特性和AVF成熟之间的相互作用。在特定目标1中，我们将在三个临床中心中的每个中心中招募40名患者，共有120名患者，他们已经参加了父级HFM队列研究。我们将在AVF创建后的2天，6周，6个月和18个月的时间内通过MRI在AVF中获得腔内几何形状和血流数据，并使用CFD建模从MRI数据中得出WSS轮廓。在特定的目标2中，我们将分析AVF创建后2天和6周的局部WSS之间的关系，随后在6和18个月时AVF管腔横截面区域的变化和血流量的变化。在特定目标3中，我们将评估先前存在的内皮功能，静脉生物力学和静脉壁形态是否是对特定目的所描述的关系的其他预测因素，混杂因素，尤其是修饰符。通过针对这些途径来支持成功成熟的创新疗法。