Vascular abnormalities in patients receiving a dialysis access.

描述(申请人提供)：与移植物相比，一旦成熟，透析瘘的存活期更长，需要更少的干预来维持长期的透析通畅。然而，20%-60%的新瘘管不能充分成熟，不适合透析。通过设置最小血管直径和确保血管通畅，术前血管标测被广泛推广，以识别适合于造瘘的血管。尽管血管标记术增加了瘘管的放置，但并不能减少未成熟的瘘管。这一令人失望的结果表明，存在影响瘘管未成熟的其他血管特性，这些特性不是通过标准的术前标测来衡量的。在一项为期3个月的先导性研究中，我们从23名接受瘘管形成的患者身上获取了动脉样本。65%(15/23)的动脉存在严重的中膜纤维化。随访6个月的14例患者中，50%(5/10)的中层纤维化组发生瘘管未成熟，而非中层纤维化组仅为0%(0/4)。中膜纤维化可能会限制瘘管形成后的动脉扩张。与无中膜纤维化的动脉相比，有中层纤维化的动脉内皮细胞血红素氧合酶-1(HO-1)的表达减少，这为血管扩张受损提供了一个潜在的机制。我们的假设是，先前存在的动脉中膜纤维化可以通过血管组织学或双功超声来识别，是CKD患者瘘管未成熟的强烈预测因素。这项资助建议测量接受瘘管的CKD患者术前动脉中膜纤维化，并将其与瘘管未成熟相关。具体地说，我们将：目标1：确定用于制造瘘管的动脉中先前存在的中层纤维化是否预示着瘘管未成熟。目的：评价动脉内膜-中层厚度(IMT)增加和血流介导的扩张减少是否是中膜纤维化的替代指标。目的：确定瘘管未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)。为了实现特定的目标，已经组建了一个多学科的团队，包括肾病学、放射学、外科和病理学。计划中的研究将：(1)在术前超声成像中测量动脉内膜厚度和血流介导的扩张；(2)手术时临床血管特征的评分；(3)用于制造瘘管的动脉的组织学中膜纤维化分级；(4)PDGF、转化生长因子-2和HO-1的血管表达评分；(5)术后超声测量瘘管血流；(6)确定瘘管是否适合透析(临床成熟)。 公共卫生相关性：在透析患者中通过手术制造瘘管，以提供一种在透析治疗期间净化血液的方法。不幸的是，大约50%的瘘管不成熟，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，以预测瘘管是否会成熟。

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.