Clinical, Hemodynamic and Biological Markers of AV Fistula Maturation

描述（由申请人提供）： 动静脉（AV）瘘不成熟目前是一个巨大的临床问题，也是血液透析人群发病和费用增加的主要原因。尽管动静脉瘘是透析通路的首选方式，但由于吻合口静脉狭窄，其成熟失败的发生率非常高。这导致多次血管内和外科手术，以及长期的导管依赖（后者通常导致败血症）。然而，尽管临床问题很严重，但我们目前无法预测哪些患者存在 AV 瘘未成熟的高风险。当前提案的中心目标是确定 AV 瘘成功或失败的预测标记。从长远来看，我们相信从这项工作中获得的机制信息将有助于开发新的疗法来促进动静脉瘘的成熟。我们计划通过一项前瞻性、队列、观察性研究来实现我们的中心目标，该研究将在 6-8 个临床中心招募多达 1200 名需要新 AV 瘘的患者。在具体目标 1 中，我们将评估临床标志物（例如人口统计、合并症、血管大小和既往血管通路史）对 AV 瘘成熟和通畅的影响。在具体目标 2 中，我们将研究血流动力学指标（如血流、体格检查、AV 吻合角度和血流动力学剪切应力与 AV 瘘管成熟之间的关系）。最后，在具体目标 3 中，我们将研究氧化应激和内皮功能等生物标志物对 AV 瘘成熟的作用。将进行逻辑回归分析以确定 AV 瘘未成熟的个体预测因子和预测因子组。我们还将利用这些数据来制定临床医生友好的“风险评分”，以便在手术前和 AV 瘘管放置后使用。我们相信，当前的提案将使我们能够将需要新透析的患者分为高风险组和低风险组。然后，高风险组的患者将要么成为积极随访和干预的目标，要么考虑采用替代形​​式的透析途径（PTFE 移植物）。展望未来，我们还希望从这项研究中获得的机制信息将使我们能够开发新的治疗干预措施，以促进动静脉瘘的成熟。这可以减少目前与动静脉瘘未成熟相关的巨大临床和经济负担。与公共卫生的相关性：更好地了解导致 AV 瘘管狭窄的因素可以让我们开发出更好的方法来预测、监测和治疗所有形式的血管狭窄，包括冠状动脉、颈动脉和外周血管疾病。

DESCRIPTION (provided by applicant): Arteriovenous (AV) fistula non-maturation is currently a huge clinical problem and a major cause of morbidity and increased costs in the hemodialysis population. Although AV fistulae are the preferred mode of dialysis access they have a very high incidence of maturation failure due to a juxta-anastomotic venous stenosis. This results in multiple endovascular and surgical procedures, together with prolonged catheter dependence (the latter often resulting in sepsis). Despite the magnitude of the clinical problem, however, we currently nave no way of predicting which patients are at high risk of AV fistula non-maturation. The central objective of the current proposal is to identify predictive markers for AV fistula success or failure. In the longer term, we believe that the mechanistic information obtained from this work, will allow for the development of novel therapies to enhance AV fistula maturation. We plan to address our central objective through a prospective, cohort, observational study which will enroll upto 1200 patients who require a new AV fistula over 6-8 clinical sites. In Specific Aim 1, we will assess the impact of clinical markers such as demographics, co-morbidities, vessel size and previous vascular access history on AV fistula maturation and patency. In Specific Aim 2, we will study the relationship between hemodynamic markers such as blood flow, physical examination, the angle of the AV anastomosis and hemodynamic shear stress on AV fistula maturation. Finally, in Specific Aim 3, we will examine the role of biological markers such as oxidative stress and endothelial function on AV fistula maturation. Logistic regression analyses will be performed to identify both individual predictors and groups of predictors for AV fistula non-maturation. We will also use this data to develop clinician friendly "risk scores" for use both prior to surgery and after AV fistula placement. We believe that the current proposal will allow us to stratify patients requiring a new dialysis access into high and low risk groups. Patients in the high risk group would then either be targeted for aggressive follow up and intervention or considered for alternate forms of dialysis access (PTFE grafts). Looking to the future, we also hope that the mechanistic information obtained from this study will allow us to develop novel therapeutic interventions to enhance AV fistula maturation. This could reduce the huge clinical and economic burden currently associated with AV fistula non-maturation. Relevance to Public Health: A better understanding of the factors responsible for AV fistula stenosis could allow us to develop better ways of predicting, monitoring and treating all forms of vascular stenosis including coronary, carotid and peripheral vascular disease.