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: 8226171
• 负责人: Amy Mottl
• 金额: $ 16.39万
• 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 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8226171
• 关键词: Albumins; Albuminuria; American; Area; 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; Commit; Complications of Diabetes Mellitus; Consultations; Continuing Education; Data; Data Analyses; Development; Development Plans; Diabetes Mellitus; Diabetic Angiopathies; 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; 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. PUBLIC HEALTH RELEVANCE: In diabetic kidney disease, the exact role of atherosclerotic and hypertensive mechanisms and methods of distinguishing them from hyperglycemic mechanisms is currently unknown. Elucidation of the relationship between diabetic microvascular complications of the eye and kidney may be helpful to discern these differences. Knowledge of the pathogenic factors of disease is crucial to development of novel therapeutics to slow or halt the progression of diabetic kidney disease.

描述（由申请人提供）：我渴望成为一名独立的学术临床医生，专注于糖尿病肾病的研究。我有一个成功的记录，我以优异的成绩毕业于东北大学，并加入了阿尔伯特·爱因斯坦医学院的阿尔法·欧米茄·阿尔法荣誉协会。我在北卡罗来纳大学（UNC）接受过肾病学和高血压学的正式培训，并获得了流行病学硕士学位。作为一名肾病专家，我的训练和经验使我对该提案中每个组成部分的生物学和临床相关性有了深入的了解。我接受过流行病学方面的培训，在生物统计方法和数据分析方面有很强的基础。我曾经是两个大型糖尿病肾病多中心试验的研究者，这让我对患者招募和遵守时间表和预算的重要性有了一个现实的看法。我之前在遗传流行病学方面的工作表明，我有能力使一个项目取得成果，并在高影响力的肾病学期刊上发表文章。通过几次经历，我改变了我的研究重点，并被糖尿病肾病不同表型的概念所吸引。该奖项将为我的研究生涯提供有保障的时间和资金，并为未来糖尿病肾病的独立和合作研究奠定基础。导师和培训计划。时来凑巧，我得到了一些世界上最杰出的糖尿病及其并发症研究人员的支持。Drs。Mauer和Klein在糖尿病肾病和视网膜病变的发病机制和流行病学方面一直处于领先地位。梅尔·戴维斯博士是美国糖尿病协会医疗保健和教育主席，也是大型多中心青年糖尿病研究搜索的联合主席。Drs。Hogan和Kshirsagar是UNC肾脏中心备受尊敬的肾脏流行病学家，他们完全致力于我的研究事业。我有巨大的机会成为SEARCH研究中不可或缺的一员，这是有史以来最大和最多样化的青年糖尿病患者群体。我的职业发展计划将提供研究设计、手稿写作和拨款准备方面的培训，并提供时间来学习对大型多中心研究（如SEARCH）成功至关重要的问题。我将得到北卡罗来纳大学肾脏病理学和眼科的共同努力他们已经同意与。Mauer和Klein在概念和技术上指导我研究糖尿病对肾脏和视网膜的病理影响。环境。北卡罗来纳大学医学院和公共卫生学院是紧密结合的环境，无论是物理上的接近还是教师之间的共生关系。它们各自都是领先的机构，汇集了技术资源和