Clinical, Hemodynamic and Biological Markers of AV Fistula Maturation

动静脉瘘未成熟是目前临床上的一大难题，也是发病率的主要原因之一。 并增加了血液透析人群的成本。尽管动静脉瘘是首选的透析方式 由于吻合口旁静脉狭窄，成熟期失败率很高。 这导致了多种血管内和外科手术，以及对导管的长期依赖。 (后者通常会导致败血症)。尽管临床问题很严重，但我们目前 没有办法预测哪些患者是房室瘘未成熟的高危人群。 当前建议的中心目标是确定预测房室瘘成功或失败的标志物。 从长远来看，我们认为，从这项工作中获得的机械性信息将使 开发促进房室瘘成熟的新疗法。我们计划实现我们的主要目标 通过一项前瞻性、队列、观察性研究，将招募多达1200名需要新AV的患者 瘘管超过6-8个临床部位。在具体目标1中，我们将评估临床标记物的影响，如 人口学、合并症、血管大小和既往血管通路病史与房室瘘成熟和 通畅性。在具体目标2中，我们将研究血流等血流动力学指标之间的关系， 房室瘘的体格检查、房室吻合口角度及血流动力学切应力 成熟。最后，在具体目标3中，我们将检查氧化应激等生物标记物的作用 血管内皮功能在房室瘘成熟过程中的作用。将进行逻辑回归分析以确定 房室瘘未成熟的个体预测因素和群体预测因素。我们还将使用这些数据来 制定临床医生友好的“风险评分”，在手术前和放置房室瘘后使用。 我们相信，目前的建议将允许我们将需要新的透析途径的患者分层为高 和低风险组。然后，高危人群中的患者将被作为积极随访的目标 和干预或考虑替代形式的透析途径(聚四氟乙烯移植物)。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出新的治疗方法 促进房室瘘成熟的干预措施。这可以减轻巨大的临床和经济负担。 目前与房室瘘未成熟有关。 与公共健康的相关性：更好地了解导致房室瘘狭窄的因素可能会 使我们能够开发更好的方法来预测、监测和治疗各种形式的血管狭窄，包括 冠状动脉、颈动脉和外周血管疾病。

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.