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，专注于糖尿病肾病的研究。我有一个成功的记录，从东北大学以最优异的成绩毕业，并进入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。我在北卡罗来纳州大学接受过肾病学和高血压方面的正式培训，并获得了流行病学硕士学位。作为一名肾病学家，我的培训和经验使我对本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着坚实的基础。我曾是两项糖尿病肾病大型多中心试验的研究者，这使我对患者招募以及遵守时间表和预算的重要性有了现实的看法。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，并在高影响力的肾脏病学期刊上发表。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。该奖项将提供受保护的时间和资金，以启动我的研究生涯，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。及时的情况使我得到了糖尿病及其并发症领域一些世界上最杰出的研究人员的支持。毛尔和克莱因博士一直是糖尿病肾病和视网膜病变发病机制和流行病学的领导者。Mayer Davis博士是美国糖尿病协会的医疗保健和教育主席，也是大型多中心青年糖尿病研究的联合主席。Hogan博士和Kshirsagar博士是肾脏病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糖尿病研究的一个组成部分，这是有史以来最大和最多样化的糖尿病青年人群。我的职业发展计划将提供研究设计、手稿撰写和资助准备方面的培训，并保护时间，以了解大型多中心研究（如ESTA）成功的核心问题。我将与肾脏病理学和眼科学的合作，他们同意与毛尔和克莱因博士一起工作，指导我研究糖尿病在肾脏和视网膜中的病理后果的概念和技术。环境医学院和公共卫生学院是紧密结合的环境，无论是在物理接近和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， 培养新兴科学家所需的各种专业知识。北卡罗来纳州转化和临床科学研究所（NC TraCS）是美国临床和转化科学奖（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;临床研究中心与支持服务;在制定提案，执行项目，生物统计学等领域的咨询;和继续教育。Research.本研究的目的是探讨糖尿病肾脏和视网膜微血管并发症之间的关系。具体而言，将分析糖尿病肾病发病机制中涉及的环境因素，以确定它们是否改变肾病和视网膜病理之间的关系。该研究计划首先分析两个现有的糖尿病患者队列，ACCORD Eye和ACCORD研究，每个研究代表不同疾病阶段的糖尿病患者。雅阁眼科研究是一项针对2型糖尿病患者的纵向研究，针对疾病进展高风险个体。视网膜病变严重程度对白蛋白尿的预测能力 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。糖尿病队列已累积5年的糖尿病病程，并将检查微量白蛋白尿和视网膜血管口径，这可能是视网膜病变的重要初始阶段。这个大型的，文化多样的青年糖尿病队列是专门设计来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包括一项初步研究，以确定对2型糖尿病参与者进行肾活检、碘海醇GFR测量和视网膜摄影的金标准的可行性。这将形成R 01的基础，R 01将这些稳健的技术扩展到更大的队列，并提供关于肾脏和眼睛的糖尿病并发症表型及其相互关系的明确数据。