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: 8512715
• 负责人: TIMMY C LEE
• 金额: $ 16.93万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 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/8512715
• 关键词: Abbreviations; Arteriovenous fistula; Biological Markers; Blood; Blood Vessels; Blood specimen; Catheters; Chronic; Chronic Kidney Failure; Clinical; Clinical Markers; 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; Health; 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; Patients; Play; Predictive Value; Prevalence; Principal Investigator; Quality of life; Reactive Oxygen Species; 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; 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）： 原发性动静脉瘘（AVF）失败，即4 - 5个月时不适合透析的AVF，仍然是增加美国AVF使用总体流行率的最重要障碍。目前没有临床或生物学标志物来预测哪些患者将经历原发性AVF失败。该项目的长期目标是开发一组来自血液和静脉组织的生物标志物，以更好地了解原发性AVF失败的机制，并将其作为临床工具来预测AVF成熟失败的高风险。本提案的近期目标重点关注氧化应激和既存静脉新生内膜增生，并将：（1）检查术前氧化应激水平、既存新生内膜增生和原发性AVF衰竭之间的关系，以及（2）研究这些新风险因素在原发性AVF衰竭病理生理学中的作用。本研究将采用前瞻性队列研究设计，招募需要植入新AVF的慢性肾脏和终末期肾脏疾病患者。将在手术前采集血液样本，并在手术时采集静脉组织样本。实现这些目标将提供关于血液和组织氧化应激水平和既存新生内膜增生在原发性AVF失败中的作用以及组织氧化应激是否与既存新生内膜增生相关的新信息。从这一建议中获得的知识将导致未来的研究，这些研究采用全身和局部给药系统进行针对氧化应激和新生内膜增生的靶向干预，以改善AVF成熟。这项研究计划将成为Timmy Lee博士五年职业发展计划的核心，并得到国际公认的血液透析血管通路狭窄专家Prabir Roy-Chaudhury博士的指导。Lee博士提出了一个职业发展计划，该计划结合了转化研究方法的教学培训，高级生物统计课程以及与理解血管通路狭窄相关的实验室培训，例如血液和静脉组织中氧化应激的测量以及人体静脉组织中的新生内膜增生。与精心挑选的合作者一起，这个职业发展计划将促进Lee博士发展成为一名成熟的临床和翻译研究者，拥有复杂研究方法和血管通路狭窄机制实验室专业知识。 公共卫生相关性：动静脉内瘘发育不良仍然是血液透析患者的一个重要问题。这项提案的工作将提高对为什么一些动静脉瘘不能充分成熟以成功用于透析以及哪些人有成熟失败的风险的理解。希望净影响将是患者生活质量的改善和患者生存率的总体提高。

项目成果

Study looks at ways to increase AVF placement. Interview by Cynthia Roberts.

研究着眼于增加 AVF 放置的方法。

• 发表时间: 2010
• 期刊: Nephrology news & issues
• 作者: Roberts,Cynthia;Lee,Timmy
• 通讯作者: Lee,Timmy

Standardized definitions for hemodialysis vascular access.

• DOI: 10.1111/j.1525-139x.2011.00969.x
• 发表时间: 2011-09
• 期刊: Seminars in dialysis
• 影响因子: 1.6
• 作者: Lee T;Mokrzycki M;Moist L;Maya I;Vazquez M;Lok CE;North American Vascular Access Consortium
• 通讯作者: North American Vascular Access Consortium

Genetic causation of neointimal hyperplasia in hemodialysis vascular access dysfunction.

血液透析血管通道功能障碍中新内膜增生的遗传因果。

• DOI: 10.1111/j.1525-139x.2011.00967.x
• 发表时间: 2012-01
• 期刊: Seminars in dialysis
• 影响因子: 1.6
• 作者: Lee T;Wadehra D
• 通讯作者: Wadehra D

"Venopathy" at work: recasting neointimal hyperplasia in a new light.

“静脉病”发挥作用：以新的视角重塑内膜增生。

• DOI: 10.1016/j.trsl.2010.07.004
• 发表时间: 2010
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Yevzlin,AlexanderS;Chan,MicahR;Becker,YolandaT;Roy-Chaudhury,Prabir;Lee,Timmy;Becker,BryanN
• 通讯作者: Becker,BryanN