Phenotypes of diabetic kidney disease and the relationship to retinal pathology

糖尿病肾病的表型及其与视网膜病理的关系

• 批准号: 8845547
• 负责人: Amy Mottl
• 金额: $ 16.77万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8845547
• 关键词: Albumins; Albuminuria; American; Area; Atherosclerosis; Award; Basic Science; Biological; Biometry; Biopsy; Biostatistical Methods; Blood Pressure; Blood Vessels; Budgets; Caliber; Cardiovascular Diseases; Cardiovascular system; Classification; Clinical; Clinical Research; Clinical Sciences; Collaborations; Collection; Complications of Diabetes Mellitus; Consultations; Continuing Education; Data; Data Analyses; Development; Development Plans; Diabetes Mellitus; Diabetic Nephropathy; Diabetic Retinopathy; Diagnosis; Disease; Disease Progression; Education; Environment; Environmental Risk Factor; Epidemiologist; Epidemiology; Ethnic Origin; Event; Excretory function; Eye; Faculty; Feasibility Studies; Foundations; Frequencies; Funding; Funding Opportunities; Future; Glomerular Filtration Rate; Goals; Gold; Grant; Healthcare; Heterogeneity; Home environment; Hyperglycemia; Hypertension; Individual; Institutes; Institution; Insulin-Dependent Diabetes Mellitus; Iohexol; Journals; Kidney; Kidney Diseases; Knowledge; Lead; Learning; Lesion; Longitudinal Studies; Manuscripts; Master' s Degree; Measurement; Measures; Mentors; Methods; Microalbuminuria; Microvascular Dysfunction; Modification; Multicenter Studies; Multicenter Trials; Nephrology; Non-Insulin-Dependent Diabetes Mellitus; North Carolina; Ophthalmology; Participant; Pathogenesis; Pathology; Pathway interactions; Patient Recruitments; Patients; Phenotype; Photography; Population Heterogeneity; Preparation; Process; Proteinuria; Public Health; Publishing; Recording of previous events; Research; Research Design; Research Personnel; Resources; Retina; Retinal; Retinal Diseases; Role; Scientist; Services; Severities; Societies; Staging; Structure of central vein of the retina; Subgroup; System; Techniques; Time; TimeLine; Training; Translational Research; Universities; Update; Urine; Vascular Diseases; Work; Writing; Youth; base; career; career development; central retinal artery; clinically relevant; cohort; design; diabetic; ethnic minority population; experience; genetic epidemiology; high risk; indexing; insight; interstitial; medical schools; member; novel; novel therapeutics; premature; retina blood vessel structure; success

DESCRIPTION (provided by applicant): I aspire to be an independent academic clinician researcher with a focus in research on diabetic kidney disease. I have a track record of success, having graduated Summa Cum Laude from Northeastern University and inducted into the Alpha Omega Alpha honor society at the Albert Einstein School of Medicine. I was formally trained in nephrology and hypertension at the University of North Carolina (UNC) and hold a master's degree in epidemiology. My training and experience as a nephrologist provides me insight to the biological and clinical relevance of every component in this proposal. Having been trained in epidemiology, I have a strong foundation in biostatistical methods and data analysis. I've been an investigator of two large multicenter trials in diabetic nephropathy giving me a realistic view of patient recruitment and the importance of adhering to timelines and budgets. My prior work in genetic epidemiology demonstrates that I am capable of bringing a project to fruition and publishing in high impact nephrology journals. Through several experiences I have changed the focus of my research and become enthralled by the concept of distinct phenotypes of diabetic kidney disease. This award will provide the protected time and funding to launch my research career and lay the foundation for future independent and collaborative research in diabetic kidney disease. Mentors and Training Plan. Timely circumstances have resulted in my being supported by some of the world's most distinguished researchers in the field of diabetes and its complications. Drs. Mauer and Klein have been leaders in the pathogenesis and epidemiology of diabetic nephropathy and retinopathy. Dr. Mayer Davis is the president of Healthcare and Education of the American Diabetes Association and co-chair of the large, multi-center SEARCH for Diabetes in Youth study. Drs. Hogan and Kshirsagar are highly esteemed renal epidemiologists at the UNC Kidney Center and are fully committed to my research career. I have the tremendous opportunity to become an integral member of the SEARCH study, the largest and most diverse population of youth with diabetes ever assembled. My career development plan will provide training in study design, manuscript writing and grant preparation and protected time to learn the issues central to the success of a large, multicenter study such as SEARCH. I will have the collaborative effort of nephropathology and ophthalmology at UNC who have agreed to work as a team with Drs. Mauer and Klein to mentor me on the concepts and techniques in studying the pathological consequences of diabetes in the kidney and retina. Environment. The UNC Schools of Medicine and Public Health are tightly integrated environments, both in physical proximity and the symbiotic relationship amongst faculty. They are each leading institutions in their own right, bringing together the technological resources and diverse array of expertise necessary for cultivating burgeoning scientists. The North Carolina Translational and Clinical Sciences Institute (NC TraCS) is home to the UNC Clinical and Translational Science Award (CTSA) and provides resources for researchers including funding opportunity updates; facilitation of collaborations; a clinical research center with support services; consultation in areas such as developing proposals, executing projects, biostatistics; and continuing education. Research. The objective of this research is to explore the relationship between diabetic microvascular complications of the kidney and retina. Specifically, environmental factors implicated in the pathogenesis of diabetic kidney disease will be analyzed to determine whether they modify the relationship between nephropathy and retinal pathology. The research plan is to first analyze two existent cohorts of patients with diabetes mellitus, the ACCORD Eye and SEARCH studies, each representing diabetics at different stages of disease. The ACCORD Eye Study is a longitudinal study of type 2 diabetics enriched for individuals at high risk of progression of disease. The predictive ability of retinopathy severity for albuminuria progression and decline in glomerular filtration rate (GFR) over four years will be analyzed. The effect of cardiovascular disease and ethnicity on this relationship will be explored. The SEARCH cohort has accumulated 5 years duration of diabetes and will be examined with regard to microalbuminuria and retinal vessel caliber, which may be important initial stages of retinopathy. This large, culturally diverse cohort of diabetes in youth is specifically designed to examine effect modification by diabetes type and ethnicity. The last component of the proposed research consists of a preliminary study to determine the feasibility of performing the gold standards of kidney biopsy, iohexol GFR measurement and retinal photography on type 2 diabetic participants. This will form the basis for an R01 which will extend these robust techniques to a larger cohort and provide definitive data regarding the phenotypes of diabetic complications of the kidney and eye and their relationship to each other.

描述（由申请人提供）：我渴望成为一名独立的学术临床研究人员，重点是研究糖尿病肾脏疾病。我有成功的记录，毕业于东北大学，并从阿尔伯特·爱因斯坦医学院（Albert Einstein Medicine）入选Alpha Omega Alpha荣誉学会。我在北卡罗来纳大学（UNC）接受了肾脏病和高血压的正式培训，并拥有流行病学硕士学位。我作为肾脏科医生的培训和经验使我深入了解本提案中每个组成部分的生物学和临床相关性。经过流行病学培训，我在生物统计学方法和数据分析方面有着强大的基础。我曾是两项糖尿病性肾病大型多中心试验的研究者，使我对患者招募和遵守时间表和预算的重要性有了现实的看法。我先前在遗传流行病学方面的工作表明，我有能力在高影响力肾脏学期刊上实现和出版项目。通过几种经验，我改变了研究的重点，并因糖尿病肾脏疾病的独特表型的概念而着迷。该奖项将提供受保护的时间和资金，以启动我的研究职业，并为未来的独立和协作糖尿病肾脏疾病奠定基础。导师和培训计划。及时的情况导致我得到了世界上一些糖尿病领域最杰出的研究人员的支持。博士。 Mauer和Klein一直是糖尿病性肾病和视网膜病的发病机理和流行病学的领导者。梅耶·戴维斯（Mayer Davis）博士是美国糖尿病协会的医疗保健和教育主席，也是大型多中心搜索糖尿病的联合主席。博士。 Hogan和Kshirsagar是UNC肾脏中心备受推崇的肾脏流行病学家，并且完全致力于我的研究生涯。我有很大的机会成为搜索研究不可或缺的成员，搜索研究是有史以来最大，最多样化的糖尿病年轻人。我的职业发展计划将提供研究设计，手稿写作和授予准备方面的培训，并保护时间，以了解大型多中心研究（例如搜索）成功的问题。我将在UNC的UNC进行肾病学和眼科的合作努力，他们同意与Drs一起工作。 Mauer和Klein指导我研究肾脏和视网膜中糖尿病的病理后果的概念和技术。环境。 UNC的医学和公共卫生学校都是紧密的环境，无论是在身体附近还是教师之间的共生关系。他们本身就是领先的机构，将技术资源和 培养新兴的科学家所需的各种专业知识。北卡罗来纳州翻译和临床科学研究所（NC TRACS）是UNC临床和转化科学奖（CTSA）的所在地，并为研究人员提供资源，包括资助机会更新；促进合作；具有支持服务的临床研究中心；在制定建议，执行项目，生物统计学等领域进行咨询；和继续教育。研究。这项研究的目的是探索肾脏和视网膜糖尿病微血管并发症之间的关系。具体而言，将分析与糖尿病肾脏疾病发病机理有关的环境因素，以确定它们是否改变了肾病与视网膜病理之间的关系。该研究计划是首先分析两名现有的糖尿病患者同类群体，即注眼和搜索研究，每个患者在不同的疾病阶段代表糖尿病患者。 Accord Eye研究是对2型糖尿病患者的纵向研究，该研究富含疾病进展的高风险的个体。视网膜病严重程度对蛋白尿的预测能力 将分析四年内肾小球滤过率（GFR）的进展和下降。将探讨心血管疾病和种族对这种关系的影响。搜索队列已经积累了5年的糖尿病持续时间，并将检查有关微量白蛋白尿和视网膜血管口径的糖尿病，这可能是视网膜病的重要初始阶段。青年中这种大型，文化上多样的糖尿病队列的专门设计，旨在检查糖尿病类型和种族的影响。拟议研究的最后一个组成部分是一项初步研究，以确定对2型糖尿病参与者进行肾脏活检，Iohexol GFR测量和视网膜摄影的黄金标准的可行性。这将构成R01的基础，R01将把这些强大的技术扩展到更大的队列，并提供有关肾脏和眼睛糖尿病并发症及其彼此关系的明确数据。