Mineral metabolism disturbances and arteriovenous fistula maturation

矿物质代谢紊乱和动静脉瘘成熟

基本信息

批准号：
8436693
负责人：
BRYAN R KESTENBAUM
金额：
$ 33.6万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-28 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8436693
关键词：
1,25 (OH) vitamin D 25-hydroxyvitamin D Affect American Applications Grants Arteries Arteriosclerosis Arteriovenous fistula Biological Markers Blood Vessels Blood flow Calcified Caliber Catheters Cell Culture Techniques Cells Cessation of life Chronic Chronic Disease Chronic Kidney Failure Clinical Dialysis patients Dialysis procedure Dihydroxycholecalciferols Electric Capacitance End stage renal failure Environment Failure Fistula Functional disorder Future Genes Gold Hemodialysis Histologic Hormones Hospitalization Hyperplasia Hypertension Incidence Individual Infection Inflammation Inflammatory Intervention Kidney Kidney Diseases Kidney Failure Kidney Transplantation Laboratories Lesion Life Link Mass Spectrum Analysis Measurement Measures Medial Mediating Metabolic Metabolic Diseases Metabolism Methods Minerals Modeling National Institute of Diabetes and Digestive and Kidney Diseases Operative Surgical Procedures Osteoblasts Outcome Parathyroid gland Pathway interactions Patients Phosphorus Physiologic pulse Physiological Postoperative Period Prevention Process Prospective Studies Renin-Angiotensin System Research Risk Risk Factors Role Sampling Series Serum Smooth Muscle Surgical Anastomosis Techniques Testing Therapeutic Intervention Thrombosis Tissues United States Vascular calcification Vasodilation Veins Venous Vitamin D arterial stiffness brachial artery calcification cardiovascular disorder risk cytokine design feeding fibroblast growth factor 23 follow-up improved metabolomics novel novel marker premature prospective research study response therapy design

项目摘要

DESCRIPTION (provided by applicant): More than 450,000 Americans have end stage kidney disease (ESKD), which requires dialysis or kidney transplantation for survival. The artriovenous fistula (AVF) represents a lifeline for hemodialysis patients because it offers substantially lower rates of infections and hospitalizations, and improved survival compared to other vascular access methods, such as artriovenous grafts or dialysis catheters. Unfortunately, as many as 50% of AVFs fail to mature within the toxic metabolic environment of kidney failure. Disturbances in mineral metabolism, which are common among ESKD patients, may be novel causes of AVF maturation failure. Early kidney disease leads to phosphorus retention, which is connected with arterial calcification in cell culture models and in individuals who have ESKD. Vascular calcification may contribute to AVF maturation failure through increased vessel stiffness and the prevention of adequate vasodilation in response to increased blood flow. Kidney dysfunction also leads to impaired vitamin D activation, which may interfere with successful AVF maturation by activating genes related to inflammation, hypertension, and thrombosis. The purpose of this application is to comprehensively evaluate associations of mineral metabolism markers with AVF maturation failure and vascular dysfunction within an established prospective study. We propose to add 6 mineral metabolism measurements to the Hemodialysis Fistula Maturation Consortium study: fibroblast growth factor-23, phosphorus, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone. We will evaluate associations of these markers with clinical AVF maturation, longitudinal changes in blood flow and vessel diameter, and cross sectional differences in endothelial function, arterial stiffness, venous compliance, and calcification. The proposed research is designed to provide credible evidence that mineral metabolism disorders contribute to vascular dysfunction and AVF maturation and suggest potential targets for future interventions designed to improve AVF maturation rates. PUBLIC HEALTH RELEVANCE: The purpose of this grant application is to add measurements of mineral metabolism biomarkers to the ongoing Hemodialysis Fistula Maturation Consortium study and to evaluate whether these markers are associated with fistula maturation and vascular dysfunction. Mineral metabolism measurements will be performed using gold- standard laboratory techniques and vascular function studies will be carried out using standardized methods. The studies proposed in this application are intended to discover new markers of fistula maturation in patients who have end stage kidney disease and to suggest possible targets for future trials.

描述（由申请人提供）：超过450,000名美国人患有末期肾脏疾病（ESKD），这需要透析或肾脏移植才能生存。脑瘘（AVF）代表血液透析患者的生命线，因为它提供了较低与其他血管通道方法（例如脑部移植物或透析导管）相比，感染和住院的发生率和生存率提高。不幸的是，在肾衰竭的有毒代谢环境中，多达50％的AVF无法成熟。在ESKD患者中常见的矿物质代谢中的障碍可能是AVF成熟衰竭的新原因。早期肾脏疾病导致磷的保留率，在细胞培养模型和患有ESKD的个体中与动脉钙化有关。血管钙化可能通过增加血管刚度和预防足够的血管舒张而导致AVF成熟失败，以应对增加的血液流量。肾功能障碍还会导致维生素D激活受损，这可能会通过激活与炎症，高血压和血栓形成有关的基因而成功地干扰AVF成熟。本应用的目的是在一项既定的前瞻性研究中全面评估矿物质代谢标志物与AVF成熟失败和血管功能障碍的关联。 We propose to add 6 mineral metabolism measurements to the Hemodialysis Fistula Maturation Consortium study: fibroblast growth factor-23, phosphorus, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone.我们将评估这些标志物与临床AVF成熟，血流和血管直径的纵向变化以及内皮功能，动脉僵硬，静脉顺应性和钙化的横截面差异的关联。拟议的研究旨在提供可靠的证据，表明矿物质代谢疾病有助于血管功能障碍和AVF成熟，并为未来旨在提高AVF成熟率的干预措施提出了潜在的目标。公共卫生相关性：该赠款应用的目的是将矿物质代谢生物标志物的测量值添加到正在进行的血液透析瘘成熟财团研究中，并评估这些标记是否与瘘管成熟和血管功能障碍有关。将使用金标准实验室技术进行矿物代谢测量，并使用标准化方法进行血管功能研究。本应用中提出的研究旨在发现患有终肾病疾病的患者的瘘管成熟的新标志，并提出可能的未来试验靶标。