Determinants of Hemodialysis AV Fistula Maturation

大约有470，000美国人患有终末期肾病，大多数人接受治疗， 血液透析。进行血液透析程序需要血管通路， 使用自体动静脉（AV）瘘、人造AV移植物或中心静脉导管。动静脉瘘是 首选血管通路类型，因为血栓形成率、感染率、通路相关 瘘管患者的医疗支出和总医疗支出都低于瘘管患者， 合成AV移植物或中心静脉导管。然而，瘘管的优点是 与之相抵消的是，瘘管的比例远远高于从未使用过的移植物 由于未能充分成熟以支持有效的血液透析，因此无法进行透析。成熟失败是 这是增加瘘管患病率的主要障碍，对许多患者来说， 手术或长期使用中心静脉导管，最不理想的血管通路类型。 最近的研究表明，20-50%的新瘘未能成熟。 本申请是对NIDDK RFA的回应，旨在建立一个设计和执行 一项针对新发瘘管患者的观察性队列研究。我们正在申请成为参与者之一 联盟的临床中心。该提案的总体目标是确定瘘管病的决定因素 成熟的结果，以便能够早期识别失败的瘘管，阐明机制 潜在的瘘管成熟，并确定促进成熟的干预措施的潜在目标。我们 建议有五个具体目标。这些包括1）确定超声作为早期诊断方法的实用性 识别未成熟的瘘管，2）评估先前存在的血管功能对瘘管的影响 瘘管成熟结局，3）确定与瘘管成熟相关的手术因素 结果，4）创建瘘管成熟的循证标准，5）表征临床 瘘管成熟失败的后果。这些目标假设招募75-100名受试者， 在我们的研究中心，600例受试者的整个研究队列的研究时间为10年。我们的几个目标包括子研究， 在受试者的子集中进行，以提供关于瘘管的额外机械信息 成熟过程 我们在血液透析血管通路方面的既定研究重点和专业知识， 作为NIDDK透析接入联盟（DAC）的临床中心， 该提案的合作者的专业知识，以及波士顿大学的可用资源，使我们 非常适合作为NIDDK计划的参与临床中心。

Approximately 470,000 Americans have end-stage renal disease and most are treated with hemodialysis. A vascular access is required for performing the hemodialysis procedure and can be provided with a native arteriovenous (AV) fistula, a synthetic AV graft; or a central venous catheter. The AV fistula is the preferred type of vascular access because thrombosis rates, infection rates, access-related expenditures, and total healthcare expenditures all are lower for patients with fistulas than for those with either synthetic AV grafts or central venous catheters. However, the advantages of fistulas are counterbalanced by the substantially higher proportion of fistulas than grafts that are never able to be used for dialysis because of failure to mature adequately to support effective hemodialysis. Maturation failure is the major barrier to increasing fistula prevalence, and, for many patients, leads to multiple surgical procedures or prolonged use of central venous catheters, the least desirable type of vascularaccess. Recent studies suggest that 20-50% of new fistulas fail to mature. This application is a response to an NIDDK RFA to establish a consortium for designing and performing an observational cohort study of patients with new fistulas. We are applying to be one of the Participating Clinical Centers of the Consortium. The overall objective of this proposal is to identify determinants of fistula maturation outcomes in order to enable early identification of failing fistulas, elucidate mechanisms underlying fistula maturation, and identify potential targets for maturation-enhancing interventions. Our proposal has five specific aims. These include 1) determining the utility of ultrasound as a method for early identification of fistulas that are failing to mature, 2) evaluating the impact of pre-existing vascular function on fistula maturation outcomes, 3) identifying surgical factors that are associated with fistula maturation outcomes, 4) creating evidence-based criteria for fistula maturation, and 5) characterizing the clinical consequences of fistula maturation failure. These aims assume an enrollment of 75-100 subjects over two years at our site for an overall study cohort of 600 subjects. Several of our aims include sub-studies that will be performed in a subset of the subjects to provide additional mechanistic information about the fistula maturation process. Our established research focus and expertise in hemodialysis vascular access, our success and leadership as a Clinical Center for the NIDDK Dialysis Access Consortium (DAC), the multidisciplinary expertise of the collaborators for this proposal, and the resources available at Boston University make us ideally suited to serve as a Participating Clinical Center for this NIDDK initiative.