Clinical, Hemodynamic and Biological Markers of AV Fistula Maturation

描述(由申请人提供)： 动静脉内瘘未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。尽管动静脉瘘是首选的透析途径，但由于吻合口旁静脉狭窄，动静脉瘘的成熟性失败率很高。这导致了多种血管内和外科手术，以及对导管的长期依赖(后者经常导致脓毒症)。然而，尽管临床问题的严重性，我们目前还无法预测哪些患者存在房室瘘未成熟的高风险。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，我们相信从这项工作中获得的机制信息将有助于开发新的治疗方法来增强房室瘘的成熟度。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个临床部位招募1200名需要新的房室瘘的患者。在具体目标1中，我们将评估临床指标，如人口统计学、合并症、血管大小和既往血管通路史对房室瘘成熟度和通畅率的影响。在具体目标2中，我们将研究血流、体格检查、房室吻合口角度等血流动力学指标与血流动力学切应力对房室瘘成熟度的影响。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在房室瘘成熟过程中的作用。将进行Logistic回归分析，以确定房室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”，用于手术前和房室瘘放置后。我们相信，目前的提议将使我们能够将需要新的透析途径的患者分为高风险组和低风险组。然后，高危人群中的患者要么接受积极的随访和干预，要么考虑接受替代形式的透析(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新的治疗措施来促进房室瘘的成熟。这可以减轻目前与房室瘘未成熟相关的巨大临床和经济负担。与公共卫生相关：更好地了解导致房室瘘狭窄的因素可以使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.