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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK093804-03
Application #
8661181
Study Section
Special Emphasis Panel (ZDK1-GRB-G (O4))
Program Officer
Rankin, Tracy L
Project Start
2012-07-15
Project End
2017-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
$168,247
Indirect Cost
$12,463
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Mottl, Amy K; Pajewski, Nicholas; Fonseca, Vivian et al. (2014) The degree of retinopathy is equally predictive for renal and macrovascular outcomes in the ACCORD Trial. J Diabetes Complications 28:874-9
Mottl, Amy K; Lu, Mei; Fine, Catherine A et al. (2013) A novel TRPC6 mutation in a family with podocytopathy and clinical variability. BMC Nephrol 14:104