Novel Biological Markers in Impaired Arteriovenous Fistula Maturation

动静脉瘘成熟受损的新型生物标志物

• 批准号: 7802943
• 负责人: TIMMY C LEE
• 金额: $ 16.75万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7802943
• 关键词: Abbreviations; Arteriovenous fistula; Biological Markers; Biological Markers; Blood; Blood Vessels; Blood specimen; Catheters; Chronic; Chronic Kidney Failure; Clinical; Cohort Studies; Complex; Coronary Arteriosclerosis; Development; Development Plans; Dialysis patients; Dialysis procedure; Disease; End stage renal failure; Epidemiologic Studies; Failure; Fistula; Fostering; Foundations; Functional disorder; Future; Glomerular Filtration Rate; Goals; Guidelines; Hemodialysis; Histology; Human; Hyperplasia; Individual; Inflammation; Intervention; Investigation; Kidney; Kidney Diseases; Knowledge; Laboratories; Lead; Lesion; Measurement; Mentorship; Multi-Institutional Clinical Trial; Nitric Oxide; Obesity; Operative Surgical Procedures; Oxidation-Reduction; Oxidative Stress; Oxidative Stress Pathway; Oxygen; Patients; Play; Predictive Value; Prevalence; Principal Investigator; Quality of life; Recruitment Activity; Reporting; Research; Research Design; Research Methodology; Research Personnel; Research Proposals; Risk; Risk Factors; Role; Staging; Stenosis; System; Systemic Therapy; Testing; Therapeutic Intervention; Time; Tissue Sample; Tissues; Training; Translational Research; United States; Venous; Woman; Work; career development; experience; high risk; improved; innovation; novel; novel marker; older patient; prospective; public health relevance; tool

DESCRIPTION (provided by applicant): Primary arteriovenous fistula (AVF) failure, AVFs that are not suitable for dialysis at four to five months, remains the most significant obstacle in increasing overall prevalence of AVF use in the United States. There are currently no clinical or biological markers to predict which patients will experience primary AVF failure. The long-term goal of this project is to develop a panel of biomarkers from blood and venous tissue to better understand the mechanisms of primary AVF failure and that will serve as clinical tools to predict AVFs at high risk for maturation failures. The immediate objectives of this proposal focus on oxidative stress and pre-existing venous neointimal hyperplasia and will: (1) examine the relationship between pre-surgical levels of oxidative stress, pre-existing neointimal hyperplasia, and primary AVF failure, and (2) study the role of these novel risk factors in the pathophysiology of primary AVF failure. This study will utilize a prospective cohort study design recruiting chronic kidney and end-stage renal disease patients requiring a new AVF placement. Blood samples will be collected prior to surgery, and venous tissue samples will be collected at the time of surgery. Accomplishing these objectives will provide new information about the role blood and tissue oxidative stress levels and pre-existing neointimal hyperplasia play in primary AVF failure, and whether tissue oxidative stress is associated with pre-existing neointimal hyperplasia. Knowledge from this proposal will lead to future studies with targeted interventions directed at modifying oxidative stress and neointimal hyperplasia using both systemic and local delivery systems in order to improve AVF maturation. This research proposal will form the core of a five-year career development plan for Dr. Timmy Lee under the mentorship of Dr. Prabir Roy-Chaudhury, an internationally-recognized expert in hemodialysis vascular access stenosis. Dr. Lee proposes a career development plan that combines didactic training in translational research methods, advanced biostatistical coursework, and laboratory training related to understanding vascular access stenosis such as measurement of oxidative stress in blood and venous tissue and neointimal hyperplasia in human venous tissue. In conjunction with carefully selected collaborators, this career development plan will foster Dr. Lee's development into an established clinical and translational investigator with expertise in complex research methodology and laboratory expertise in mechanisms of vascular access stenosis. PUBLIC HEALTH RELEVANCE: Poor arteriovenous fistula development remains a significant problem among hemodialysis patients. The work from this proposal will improve the understanding of why some arteriovenous fistulas do not mature adequately for successful use on dialysis and which individuals are at risk for maturation failures. The net impact will, hopefully, be an improvement in patient quality of life and an overall increase in patient survival.

描述（由申请人提供）： 初级动静脉瘘（AVF）衰竭，不适合在四到五个月时透析的AVF仍然是增加美国AVF使用的总体流行率的最重要障碍。目前尚无临床或生物学标记来预测哪些患者将遇到主要的AVF衰竭。该项目的长期目标是开发一个从血液和静脉组织的生物标志物小组，以更好地了解原发性AVF衰竭的机制，并将作为预测具有高度成熟失败风险的AVF的临床工具。该提案的直接目标集中于氧化应激和静脉前静脉新临床增生，并将：（1）检查氧化应激的术前水平之间的关系，预先存在的新内膜增生和原发性AVF失败和（2）研究这些新型危险因素在原发性AVF的病理学中的作用。这项研究将利用一项前瞻性队列研究设计，招募了需要新的AVF放置的慢性肾脏和末期肾脏疾病患者。手术前将收集血液样本，并在手术时收集静脉组织样品。实现这些目标将提供有关血液和组织氧化应激水平的作用的新信息，并在原发性AVF失败中起作用的新内膜增生，以及组织氧化应激是否与现有的新内膜增生有关。该提案的知识将导致未来的研究，其针对性的干预措施旨在使用全身和局部递送系统来改变氧化应激和新内膜增生，以改善AVF成熟。这项研究建议将在蒂姆·李博士（Timmy Lee）博士的指导下为蒂姆·李（Timmy Lee）博士提供五年职业发展计划，这是Prabir Roy-Chaudhury博士的指导。李博士提出了一项职业发展计划，该计划在翻译研究方法，高级生物统计学课程以及与了解血管通道狭窄有关的实验室培训中结合了教学训练，例如测量血液和静脉组织中的氧化应激以及人类静脉组织中的新内膜增生。该职业发展计划与精心挑选的合作者一起，将李博士的发展促进既定的临床和转化研究者，具有复杂的研究方法论和血管通道狭窄机制的实验室专业知识方面的专业知识。 公共卫生相关性：血液透析患者的动静脉瘘发育仍然是一个重大问题。该提案的工作将提高人们对为什么某些动静脉瘘并不能充分成熟以成功地使用透析以及哪些人面临成熟失败的风险的理解。希望净影响能够改善患者的生活质量和患者生存的总体增长。