Vascular abnormalities in patients receiving a dialysis access.

描述（由申请人提供）：与移植物相比，一旦成熟，透析瘘管有更长的生存期，并且需要更少的干预来维持长期的透析通畅。然而，20-60%的新瘘管未成熟到适合透析。术前血管测绘被广泛推广，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。虽然血管测绘增加了瘘管的位置，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，而这些特性在标准的术前制图中无法测量。在为期3个月的初步研究中，我们从23名接受造瘘术的患者身上获得了动脉标本。65%（15/23）的动脉存在严重的内侧纤维化。在14例bbb6个月的随访中，50%（5/10）的内侧纤维化患者发生瘘管不成熟，而没有内侧纤维化的患者为0%（0/4）。内侧纤维化可能限制造瘘后动脉扩张。内皮血红素加氧酶-1 （HO-1）在动脉内侧纤维化中表达降低，与动脉内侧无纤维化相比，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超声识别，是CKD患者瘘管未成熟的一个强有力的预测因素。该资助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：目的1：确定用于制造瘘管的动脉中先前存在的内侧纤维化是否预测瘘管未成熟。目的2：评估术前超声显示动脉内膜-中膜厚度（IMT）增加和血流介导扩张减少是否为内侧纤维化的替代标志。目的3：确定瘘不成熟是否与血管活性物质的表达改变有关，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）。为了达到特定的目的，我们组建了一个多学科的团队，包括肾脏病学、放射学、外科和病理学。计划的研究将：(1)在术前超声测绘期间测量动脉的IMT和血流介导的扩张；(2)对手术时血管特征进行临床评分；(3)用于造瘘的动脉的组织学分级内侧纤维化；(4)检测血管中PDGF、TGF-2、HO-1的表达；(5)术后超声测量瘘血流量；(6)确定瘘管是否适合透析（临床成熟度）。

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).