Anatomic and functional predictors of arteriovenous fistula maturation

描述（由申请人提供）： 功能良好的动静脉内瘘是长期血液透析的首选血管通路类型。在最近的DAC瘘管研究中，我们和其他人观察到，不到16%的手术创建的瘘管因血栓形成而失败，但超过60%的瘘管未能达到透析的适用性，证实成熟受损是瘘管创建后成功的主要障碍。该提案将解决瘘管成熟知识方面的根本空白。该建议的主要假设是，上肢动脉和静脉循环的解剖和功能异常的组合预测4期和5期慢性肾脏疾病患者的动静脉瘘成熟失败。我们认为，血管结构和功能的研究可以用来预测瘘的成熟。我们进一步假设，手臂血管钙化通过损害血管扩张性和内皮依赖性血管舒张，易导致瘘管成熟失败。此外，我们认为交感神经介导的血管收缩增强是导致瘘成熟失败的另一个因素，因为它阻止了发展中动静脉瘘所需的血流量的大幅增加。为了验证这些假设，我们将对慢性肾脏疾病患者的瘘管成熟进行前瞻性观察研究。我们将定义瘘管成熟的自然史和相关的临床和手术事件。我们将对血管解剖结构、手臂血流和血管钙化进行详细的术前评估，以确定瘘成熟的术前预测因素。最后，在瘘管形成后的早期，我们将评估瘘管解剖结构、血流和体格检查结果，以制定瘘管成熟受损的早期术后预测因素。从本提案中的研究中获得的知识将有助于改善动静脉瘘创建的患者选择，确定成熟失败的关键解剖和功能预测因素，并为未来促进瘘成熟的干预试验提供有效数据。功能良好的血管通路是为接受血液透析的患者提供维持生命治疗的绝对必要条件。AV瘘是透析的最佳血管通路类型，但不幸的是，大多数瘘未能充分发展以维持透析治疗。该提案旨在确定瘘管病失败的预测因素，以便将来可以实施适当的干预措施来提高成功率。

DESCRIPTION (provided by applicant): A well functioning arteriovenous fistula is the preferred type of vascular access for chronic hemodialysis. In the recent DAC fistula studies we and others observed that fewer than 16% of surgically created fistulas failed due to thrombosis but more than 60% of fistulas failed to reach suitability for dialysis, confirming that impaired maturation is the main obstacle to success after fistula creation. This proposal will address fundamental gaps in knowledge about fistula maturation. The main hypothesis of this proposal is that a combination of anatomic and functional abnormalities of the arterial and venous circulations of the upper extremities predict AV fistula maturation failure in patients with stage 4 and 5 chronic kidney disease. We submit that studies of vascular structure and function can be used to predict fistula maturation. We further hypothesize that vascular calcification in the arm predisposes to fistula maturation failure by impairing vascular distensibility and endothelium-dependent vasodilation. In addition, we propose that augmented sympathetic-mediated vasoconstriction is another factor that contributes to maturation failure of fistulas by preventing the large increases in blood flow necessary in a developing AV fistula. To test these hypotheses we will conduct a prospective observational study of fistula maturation in patients with chronic kidney disease. We will define the natural history of fistula maturation and related clinical and surgical events. We will perform a detailed preoperative evaluation of vessel anatomy, blood flow to the arm and vascular calcifications to identify preoperative predictors of fistula maturation. Finally, early after fistula creation we will evaluate fistula anatomy, blood flow and physical examination findings to develop early postoperative predictors of impaired fistula maturation. Knowledge obtained from the studies in this proposal will help to improve patient selection for AV fistula creation, identify key anatomic and functional predictors of maturation failure, and provide valid data for future intervention trials to promote fistula maturation. A well functioning vascular access is an absolute necessity to provide life-sustaining treatments for patients on hemodialysis AV fistulas are the best type of vascular access for dialysis, but unfortunately, most fistulas fail to develop adequately to sustain dialysis treatments. This proposal aims to identify predictors of fistula failure so that appropriate interventions to improve success can be implemented in the future.