Novel Biomarkers in Interstitial Fibrosis/Tubular Atrophy in Kidney Transplants

肾移植中间质纤维化/肾小管萎缩的新型生物标志物

• 批准号: 7713030
• 负责人: Sanjeev Kumar Akkina
• 金额: $ 15.37万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7713030
• 关键词: Acute; Allografting; Angiotensin II Receptor; Atrophic; Biochemical Markers; Bioinformatics; Biological Markers; Biopsy; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Confounding Factors (Epidemiology); Data; Deterioration; Development; Development Plans; Diagnosis; Dialysis procedure; Disease Management; Double-Blind Method; End stage renal failure; Enrollment; Environment; Event; Fibrosis; Functional disorder; Future; Goals; Hypertension; Incidence; Injury; Kidney; Kidney Diseases; Kidney Failure; Kidney Transplantation; Life; Mass Spectrum Analysis; Measures; Medical; Mentors; Methods; Minnesota; Monitor; Nephrology; Placebo Control; Primary Prevention; Proteins; Proteinuria; Proteomics; Protocols documentation; Randomized; Research; Research Design; Research Personnel; Sampling; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staging; Techniques; Therapeutic; Thick; Time; Training Programs; Transplant Recipients; Transplantation; Tubular formation; Universities; Urinary tract; Urine; blood pressure regulation; career development; cerebral atrophy; clinical practice; falls; graft function; innovation; insight; interest; interstitial; kidney allograft; novel; prevent; statistics; success; urinary

DESCRIPTION (provided by applicant): The applicant is a nephrology fellow interested in studying kidney disease using proteomic techniques that can be transitioned into clinical practice to aid with diagnosis and disease management. The applicant's long-term goal is to successfully use proteomics to identify early markers of kidney disease that he can use to better understand mechanisms of kidney disease and halt progression to end-stage kidney disease. This application proposes a career development plan that will transition the applicant to an independent investigator in proteomics and kidney disease. Briefly, the training program of the application includes formal coursework in the fields of statistics, bioinformatics, and clinical trial design while incorporating mentored guidance from Dr. Hassan Ibrahim, Division of Renal Diseases and Hypertension and Dr. Gary Nelsestuen, Director of the Center for Mass Spectrometry and Proteomics at the University of Minnesota. The applicant also outlines the outstanding environment at the University of Minnesota for career development and research. The immediate goal of the applicant is to identify urinary markers of interstitial fibrosis/tubular atrophy (IF/TA) in the kidney allograft, a major problem in transplantation leading to graft loss. The applicant proposes to study this by studying two groups of kidney transplant recipients at the University of Minnesota. The first group includes a 154 kidney transplant recipients enrolled in a clinical trial looking specifically at IF/TA. This study has prospectively collected urine samples over 5 years specifically for future proteomic studies such as the one proposed. The second group includes kidney transplant recipients with graft deterioration and renal biopsy data for correlative analyses. The applicant proposes to use matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and ITRAQ analyses to do focused studies on the urine for biomarkers implicated in IF/TA. The applicant, under the guidance of Dr. Nelsestuen, has shown early data suggesting these techniques to be effective in following stable transplant recipients and that these techniques can detect changes in proteins associated with graft deterioration. RELEVANCE: The results of this study will provide further insight into IF/TA and provide biomarkers that may assist clinicians in treating a growing problem in kidney transplantation.

描述（由申请人提供）：申请人是一个有兴趣使用蛋白质组学技术研究肾脏疾病的肾脏病学者，可以将其转变为临床实践，以帮助诊断和疾病管理。申请人的长期目标是成功使用蛋白质组学来识别他可以用来更好地理解肾脏疾病机制的早期标记，并停止肾脏疾病的机制。该申请提出了一项职业发展计划，该计划将把申请人转换为蛋白质组学和肾脏疾病的独立研究者。简而言之，该申请的培训计划包括统计，生物信息学和临床试验设计领域的正式课程，同时纳入了Hassan Ibrahim博士的指导，肾脏疾病和高血压部以及MinSestota大学的质谱和蛋白质组学中心总监Gary Nelsestuen博士。申请人还概述了明尼苏达大学职业发展和研究的杰出环境。申请人的直接目标是鉴定肾脏同种异体移植物中间质纤维化/管状萎缩（IF/TA）的尿标志物，这是移植导致移植物损失的主要问题。申请人建议通过研究明尼苏达大学的两组肾脏移植接受者来研究这一点。第一组包括参加临床试验的154个肾脏移植接受者，专门研究IF/TA。这项研究已在5年内专门针对未来的蛋白质组学研究（例如提出的）收集了尿液样本。第二组包括具有移植物恶化的肾脏移植受者和用于相关分析的肾脏活检数据。申请人建议使用矩阵辅助激光解吸/电离飞行时间（MALDI-TOF）和ITRAQ分析来对涉及IF/TA的生物标志物进行重点研究。在Nelsestuen博士的指导下，申请人显示了早期数据，表明这些技术有效遵循稳定的移植受者，并且这些技术可以检测与移植物降低相关的蛋白质变化。 相关性：这项研究的结果将为IF/TA提供进一步的见解，并提供可能有助于临床医生治疗肾脏移植中日益增长的问题的生物标志物。