This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetic nephropathy (DN) is the leading cause of chronic renal disease in the world. Though some modifiable risk factors have been identified, data from Caucasians and Pima Indians indicate that DN is genetically determined. The investigators hypothesize that the intermediate phenotypes, proteinuria and glomerular filtration rate (GFR) change, which respectively predict and measure progression of diabetic nephropathy to End-Stage Renal Disease (ESRD), are heritable. The hypothesis will be tested in a longitudinal study of African American (AA) and Caucasian families, which will permit the natural history of DN in AA to be defined for the first time. Data will be generated by quantitative trait locus (QLA) analysis, which offers advantages to the ongoing strategies, including enrollment and better definition of the clinical course of DN subjects with intermediate phenotypes (e.g. microalbuminuria), which have previously been excluded in genetic analyses. Their diabetic siblings will be phenotyped and followed longitudinally. Dependent outcomes will include yearly urine albumin excretion and GFR measurements. Target accrual is 900 subjects with 450 at MetroHealth Medical Center.
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