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: 8106051
• 负责人: Scott A Berceli
• 金额: $ 72.16万
• 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/8106051
• 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. PUBLIC HEALTH RELEVANCE: The safest path for blood to flow from the patient to a dialysis machine and back, a veritable lifeline for a dialysis patient, is created by surgically connecting the patient's own artery to vein. This path is known as a native fistula, which enlarges ("matures") after surgery to allow increased blood flow and has fewer long-term complications than other types of hemodialysis pathways, but, unfortunately, a majority of native fistulas do not properly mature after surgical creation. This study will examine why these conduits do not mature, and the knowledge gained should suggest new strategies to promote fistula maturation and improve the prospects of dialysis patients.

描述(申请人提供)：功能性动静脉瘘(AVF)是慢性血液透析的首选血管通路。然而，高达60%的动静脉瘘永远不成熟，即达到足够的管腔扩张，以允许足够的血流速度用于慢性透析。NIDDK最近成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名患者的队列研究来调查这一问题。HFM队列研究将确定AVF成熟失败的预测因素，并收集关于机械性假说的间接证据。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更广泛的调查。我们建议在三个HFM临床中心和DCC进行一项HFM辅助研究，以检验异常血流动力学在AVF成熟失败的发病机制中的作用。虽然血流动力学壁切应力(WSS)的改变被认为是调节血管重构和新生内膜增生形成的因素，但WSS在AVF发展过程中的空间分布及其与AVF成熟之间的关系目前尚不清楚。此外，WSS对AVF管腔的影响可能受AVF产生前血管壁的预先存在的属性的影响。以前关于动静脉瘘患者WSS的研究很少，也没有研究WSS、既往的血管壁特性和AVF预后之间的关系。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，随着时间的推移收集开发动静脉瘘的WSS数据，并将这些信息与母公司HFM研究中收集的血管壁特性数据联系起来。通过这种联系，我们将能够研究随着时间的推移WSS、血管壁特性和AVF成熟之间的相互作用。在具体目标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，他们已经参加了母公司HFM队列研究。在AVF建立后2天、6周、6个月和18个月分别通过MRI获得AVF的管腔几何形状和血流数据，并通过CFD建模从MRI数据中获得WSS轮廓。在具体目标2中，我们将分析AVF建立后2天和6周的局部WSS与6个月和18个月时AVF管腔横截面积和血流速度变化的关系。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测量是否是特定目标2中描述的关系的附加预测因子、混杂因子，或者特别是修饰符。阐明血流动力学和先前存在的血管壁特性与AVF结局的相互作用将导致AVF成熟的新的预测因子，阐明AVF失败的关键途径，并通过靶向这些途径指向支持成功成熟的创新疗法。 与公共健康相关：血液从患者流向透析机并返回的最安全路径，是透析患者名副其实的生命线，通过手术将患者自己的动脉与静脉连接起来。这种途径被称为自然内瘘，手术后会扩大(“成熟”)以增加血流量，并且与其他类型的血液透析途径相比，其长期并发症较少，但不幸的是，大多数自然内瘘在手术后并未完全成熟。这项研究将研究为什么这些管道不成熟，所获得的知识应该会建议新的策略，以促进瘘管成熟和改善透析患者的前景。