Determinants of Hemodialysis AV Fistula Maturation

描述（由申请人提供）： 大约有47万美国人患有终末期肾病，大多数人接受血液透析治疗。进行血液透析手术需要血管通路，可提供自体动静脉（AV）瘘、人工AV移植物或中心静脉导管。动静脉瘘是首选的血管通路类型，因为动静脉瘘患者的血栓形成率、感染率、通路相关费用和总医疗费用均低于人工动静脉移植物或中心静脉导管患者。然而，瘘管的优势被瘘管的比例显著高于移植物所抵消，因为移植物未能充分成熟以支持有效的血液透析，因此无法用于透析。成熟失败是增加瘘管患病率的主要障碍，并且对于许多患者，导致多次外科手术或长期使用中心静脉导管，这是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，旨在建立一个联盟，以设计和执行新发瘘管患者的观察性队列研究。我们正在申请成为联盟的参与临床中心之一。本申请的总体目标是确定瘘管成熟结果的决定因素，以便能够早期识别失败的瘘管，阐明瘘管成熟的潜在机制，并确定促进成熟干预的潜在目标。我们的申请有五个具体目标。这些包括1）确定超声作为早期识别未能成熟的瘘管的方法的效用，2）评价预先存在的血管功能对瘘管成熟结局的影响，3）确定与瘘管成熟结局相关的手术因素，4）创建瘘管成熟的循证标准，以及5）表征瘘管成熟失败的临床后果。这些目标假设我们的研究中心在两年内招募75-100例受试者，整个研究队列为600例受试者。我们的几个目标包括将在受试者子集中进行的子研究，以提供有关瘘管成熟过程的额外机制信息。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，我们作为NIDDK透析通路联盟（DAC）临床中心的成功和领导地位，合作者针对该应用的多学科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倡议的参与临床中心。

DESCRIPTION (provided by applicant): 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 application 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 application 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 application, and the resources available at Boston University make us ideally suited to serve as a Participating Clinical Center for this NIDDK initiative.