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，透析瘘管的存活时间更长，维持透析长期通畅所需的干预更少。然而，20-60%的新瘘管不能充分成熟以适合透析。广泛推广术前血管标测，通过设定最小血管直径和确保血管通畅性来识别适合于瘘管创建的血管。虽然血管标测增加了瘘的位置，但它并没有减少瘘的不成熟。这一令人失望的结果表明，存在影响瘘未成熟的其他血管特性，而这些特性不能通过标准术前标测来测量。在一项为期3个月的初步研究中，我们从23名接受瘘管创建的患者中获得动脉标本。65%（15/23）的动脉存在严重的中膜纤维化。在14例随访时间>6个月的患者中，50%（5/10）的中膜纤维化患者发生瘘未成熟，而无中膜纤维化的患者为0%（0/4）。中膜纤维化可能限制瘘形成后的动脉扩张。与无中膜纤维化的动脉相比，中膜纤维化的动脉中内皮血红素氧合酶-1（HO-1）表达降低，为血管舒张受损提供了潜在机制。我们的假设是，预先存在的动脉中膜纤维化，可以通过血管组织学或多普勒超声识别，是CKD患者瘘未成熟的强有力预测因子。 该资助计划测量接受瘘管的CKD患者的术前动脉中膜纤维化，并将其与瘘管未成熟联系起来。具体而言，我们将：目标1：确定用于创建瘘的动脉中预先存在的中膜纤维化是否可预测瘘未成熟。目标二：评价术前超声显示的动脉内膜中层厚度（IMT）增加和血流介导的扩张减少是否是中膜纤维化的替代标志物。目标3：确定瘘管不成熟是否与血管活性物质表达改变相关，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）。 为了实现特定的目标，一个多学科的团队已经组装，包括肾脏病学，放射学，外科和病理学。计划的研究将：（1）在术前超声标测期间测量动脉的IMT和血流介导的扩张;（2）在手术时临床上对血管特征进行评分;（3）对用于创建瘘的动脉中的组织学中膜纤维化进行分级;（4）对PDGF、TGF-2和HO-1的血管表达进行评分;（5）通过超声测量术后瘘血流;和（6）确定瘘管对透析的适合性（临床成熟）。 公共卫生相关性：瘘管是通过手术在透析患者体内形成的，目的是在透析治疗期间提供一种净化血液的方法。不幸的是，大约50%的瘘管没有成熟，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，预测瘘是否会成熟。

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.