Phenotypes of diabetic kidney disease and the relationship to retinal pathology

个人描述(申请人提供)：我立志成为一名独立的学术临床研究员，专注于糖尿病肾脏疾病的研究。我有成功的记录，以优异的成绩从东北大学毕业，并被阿尔伯特·爱因斯坦医学院的Alpha Omega Alpha荣誉学会录用。我在北卡罗来纳大学(UNC)接受过肾病学和高血压方面的正式培训，并拥有流行病学硕士学位。作为一名肾科医生，我的培训和经验使我对这项建议中每个组成部分的生物学和临床相关性有了深入的了解。我受过流行病学培训，在生物统计学方法和数据分析方面有很强的基础。我是糖尿病肾病两个大型多中心试验的研究员，这让我对患者招募以及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，我有能力实现一个项目，并在高影响力的肾脏病学杂志上发表文章。通过几次经历，我改变了我的研究重点，并被糖尿病肾病的不同表型的概念迷住了。这一奖项将为我开始研究生涯提供有保障的时间和资金，并为未来糖尿病肾脏疾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。Mauer博士和Klein博士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。迈耶·戴维斯博士是美国糖尿病协会医疗保健和教育部门的主席，也是大型多中心青年糖尿病研究项目的联合主席。霍根博士和克希尔萨加博士是北卡罗来纳大学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。我有极大的机会成为SEARCH研究中不可或缺的一员，这是有史以来聚集的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、手稿写作和赠款准备方面的培训，并提供受保护的时间来学习大型、多中心研究(如搜索)成功的核心问题。我将与北卡罗来纳大学的肾脏病理学和眼科医生合作，他们已经同意与Mauer博士和Klein博士作为一个团队来指导我研究糖尿病对肾脏和视网膜的病理后果的概念和技术。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，无论是在物理上的接近还是教职员工之间的共生关系。它们各自都是领先的机构，汇聚了技术资源和 培养初出茅庐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)是北卡罗来纳州大学临床和翻译科学奖(CTSA)的所在地，为研究人员提供资源，包括资助机会更新；促进合作；一个具有支持服务的临床研究中心；在制定提案、执行项目、生物统计和继续教育等领域的咨询。研究。本研究的目的是探讨糖尿病肾脏微血管并发症与视网膜的关系。具体地说，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了肾病和视网膜病理之间的关系。这项研究计划首先分析现有的两个糖尿病患者队列，ACCORD EYE和SEARCH研究，每个研究代表不同疾病阶段的糖尿病患者。ACCORD Eye研究是一项针对2型糖尿病患者的纵向研究，该研究针对疾病进展的高风险人群。视网膜病变严重程度对蛋白尿的预测能力 将分析四年来肾小球滤过率(GFR)的进展和下降。我们将探讨心血管疾病和种族对这种关系的影响。研究队列已经累积了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。这一庞大的、不同文化的青年糖尿病队列是专门为检查糖尿病类型和种族的效果改变而设计的。这项拟议研究的最后一部分包括初步研究，以确定在2型糖尿病参与者身上进行肾活检、碘海醇GFR测量和视网膜摄影的黄金标准的可行性。这将形成R01的基础，R01将把这些强大的技术扩展到更大的队列，并提供关于糖尿病肾脏和眼睛并发症的表型及其相互关系的明确数据。

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.