Vascular abnormalities in patients receiving a dialysis access.

接受透析的患者的血管异常。

• 批准号: 8296317
• 负责人: MICHAEL ALLON
• 金额: $ 34.95万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8296317
• 关键词: Affect; Anastomosis - action; Arterial Intimas; Arteries; Blood; Blood Vessels; Blood flow; Caliber; Characteristics; Chronic Kidney Failure; Clinical; Dialysis patients; Dialysis procedure; End stage renal failure; Ensure; Fibrosis; Figs - dietary; Fistula; Frequencies; Goals; Grant; Hemodialysis; Histologic; Histology; Intervention; Maps; Measures; Medial; Mediating; Molecular; Nephrology; Operative Surgical Procedures; Outcome; Pathology; Patients; Pilot Projects; Platelet-Derived Growth Factor; Property; Radiology Specialty; Specimen; Surrogate Markers; Thick; Time; Transforming Growth Factor beta; Ultrasonography; Vasodilation; Veins; follow-up; heme oxygenase-1; insight; intima media; multidisciplinary; public health relevance; standard measure

DESCRIPTION (provided by applicant): Once they mature, dialysis fistulas have longer survival and require fewer interventions to maintain long-term patency for dialysis, as compared with grafts. However, 20-60% of new fistulas fail to mature adequately to be suitable for dialysis. Preoperative vascular mapping is widely promoted to identify vessels suitable for fistula creation, by setting minimum vascular diameters and ensuring vessel patency. Although vascular mapping increases fistula placement, it does not decrease fistula non- maturation. This disappointing outcome suggests the existence of additional vascular properties affecting fistula immaturity, which are not measured by standard preoperative mapping. During a 3- month pilot study, we obtained arterial specimens from 23 patients undergoing fistula creation. Severe medial fibrosis was present in 65% (15/23) of the arteries. In 14 patients with >6 months of follow-up, fistula non-maturation occurred in 50% (5/10) of patients with medial fibrosis vs. 0% (0/4) of those without medial fibrosis. Medial fibrosis may limit arterial dilation after fistula creation. Endothelial heme oxygenase-1 (HO-1) expression was decreased in arteries with medial fibrosis, as compared to arteries without medial fibrosis, providing a potential mechanism for impaired vasodilation. Our hypothesis is that preexisting arterial medial fibrosis, which can be identified by vascular histology or by duplex ultrasound, is a strong predictor of fistula non-maturation in CKD patients. This grant proposes to measure preoperative arterial medial fibrosis in CKD patients receiving a fistula, and correlate it with fistula non-maturation. Specifically, we will: Aim 1: Determine whether preexisting medial fibrosis in the artery used to create a fistula is predictive of fistula non-maturation. Aim 2: Evaluate whether increased arterial intima-media thickness (IMT) and decreased flow- mediated dilation on preoperative ultrasound are surrogate markers of medial fibrosis. Aim 3: Determine whether fistula non-maturation is associated with altered expression of vasoactive substances, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-2), and heme oxygenase-1 (HO-1). To achieve the specific aims, a multidisciplinary team has been assembled, consisting of nephrology, radiology, surgery, and pathology. Planned studies will: (1) measure the IMT and flow-mediated dilation of the arteries during preoperative ultrasound mapping; (2) score vessel characteristics clinically at the time of surgery; (3) grade histologically medial fibrosis in the artery used to create the fistula; (4) score vascular expression of PDGF, TGF-2, and HO-1; (5) measure fistula blood flow postoperatively by ultrasound; and (6) determine fistula suitability for dialysis (clinical maturation). PUBLIC HEALTH RELEVANCE: Fistulas are created surgically in dialysis patients to provide a way to purify blood during dialysis treatments. Unfortunately, about 50% of fistulas don't mature, and therefore cannot be used for dialysis. The goal of this study is to identify abnormalities of the arteries and veins that predict whether a fistula will mature.

描述（由申请人提供）：与移植物相比，一旦成熟，透析瘘管的存活时间更长，并且需要更少的干预措施来维持透析的长期通畅。然而，20-60% 的新瘘管未能充分成熟，不适合透析。术前血管标测被广泛推广，通过设定最小血管直径和确保血管通畅来识别适合造瘘的血管。尽管血管标测增加了瘘管的放置，但它并没有减少瘘管的不成熟。这一令人失望的结果表明存在影响瘘管不成熟的额外血管特性，而标准术前标测无法测量这些特性。在为期 3 个月的试点研究中，我们从 23 名接受造瘘术的患者身上获取了动脉标本。 65% (15/23) 的动脉存在严重的内侧纤维化。在 14 名随访超过 6 个月的患者中，50% (5/10) 的内侧纤维化患者发生瘘管未成熟，而无内侧纤维化患者的这一比例为 0% (0/4)。内侧纤维化可能会限制瘘管形成后的动脉扩张。与没有内侧纤维化的动脉相比，有内侧纤维化的动脉中内皮血红素加氧酶-1（HO-1）的表达降低，这提供了血管舒张受损的潜在机制。我们的假设是，预先存在的动脉内侧纤维化（可以通过血管组织学或双功能超声识别）是 CKD 患者瘘管不成熟的强有力的预测因子。 该拨款计划测量接受瘘管的 CKD 患者术前动脉内侧纤维化，并将其与瘘管未成熟相关联。具体来说，我们将： 目标 1：确定用于创建瘘管的动脉中预先存在的内侧纤维化是否可以预测瘘管不成熟。目标 2：评估术前超声显示的动脉内膜中层厚度 (IMT) 增加和血流介导扩张减少是否是中层纤维化的替代标志。目标 3：确定瘘管未成熟是否与血管活性物质的表达改变相关，包括血小板衍生生长因子 (PDGF)、转化生长因子-β (TGF-2) 和血红素加氧酶-1 (HO-1)。 为了实现具体目标，我们组建了一个多学科团队，包括肾脏病学、放射学、外科和病理学。计划的研究将：（1）在术前超声测绘过程中测量 IMT 和血流介导的动脉扩张； (2)对手术时的临床血管特征进行评分； (3) 用于建立瘘管的动脉的组织学内侧纤维化分级； (4)血管内PDGF、TGF-2、HO-1表达评分； (5)术后超声测量瘘管血流量； (6) 确定瘘管是否适合透析（临床成熟度）。 公众健康相关性：通过手术在透析患者身上制造瘘管，以提供在透析治疗期间净化血液的方法。不幸的是，大约 50% 的瘘管尚未成熟，因此不能用于透析。这项研究的目的是确定动脉和静脉的异常情况，以预测瘘管是否会成熟。