Clinical, Hemodynamic and Biological Markers of AV Fistula Maturation

描述（由申请人提供）： 动静脉（AV）内瘘不成熟是目前一个巨大的临床问题，也是血液透析人群发病率和费用增加的主要原因。尽管动静脉瘘是透析通路的首选模式，但由于近吻合静脉狭窄，动静脉瘘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性（后者通常导致败血症）。尽管临床问题的严重性，但是，我们目前还没有办法预测哪些患者是动静脉瘘未成熟的高风险患者。本提案的中心目标是确定动静脉瘘成功或失败的预测标志物。从长远来看，我们相信从这项工作中获得的机制信息，将允许开发新的治疗方法，以提高动静脉瘘的成熟。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家临床试验机构招募多达1200例需要新动静脉瘘的患者。在具体目标1中，我们将评估临床标志物（如人口统计学、共病、血管尺寸和既往血管通路史）对动静脉瘘成熟和通畅的影响。在特定目标2中，我们将研究血流动力学标志物（如血流量、体格检查、AV吻合角度和血流动力学切应力）与AV瘘成熟之间的关系。最后，在具体目标3中，我们将研究生物标志物如氧化应激和内皮功能对动静脉瘘成熟的作用。将进行逻辑回归分析，以确定动静脉瘘未成熟的个体预测因素和预测因素组。我们还将使用这些数据来开发临床医生友好的“风险评分”，用于术前和动静脉瘘放置后。我们认为，目前的提案将使我们能够将需要新透析通路的患者分为高风险组和低风险组。然后，高风险组的患者将成为积极随访和干预的目标，或考虑采用替代形式的透析通路（PTFE移植物）。展望未来，我们也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，以提高动静脉瘘的成熟。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：更好地了解动静脉瘘狭窄的因素可以使我们开发更好的方法来预测，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.