application) This proposal for career development award for Lynda Szczech, MD will provide the didactic training and research experience necessary to make her a competitive and productive clinical investigator in the field of HIV-associated nephropathy (HIVAN). This proposal focuses on the epidemiology of HIV associated nephropathy (HIVAN). HIVAN is a complication of HIV infection that is associated with a 50% annual mortality. As demonstrated by the United States Renal Data Service, HIVAN is now the fourth leading cause of end-stage renal disease in African-Americans aged 20 to 64. This study will provide vital information on the risk factors and clinical course of this kidney disease that may be used subsequently to design strategies for prevention and treatment. This study will utilize a cross-sectional survey to study a large, population-based sample of HIV-infected patients to determine the prevalence of microalbuminuria and proteinuria and the risk factors for the development of HIVAN. The cohort of patients with microalbuminuria will be followed prospectively along with a sample of patients without evidence of renal disease to determine if the presence of microalbuminuria is predictive for the development of nephropathy or other outcomes such as mortality. Determination of the natural history of microalbuminuria may subsequently provide a noninvasive means to detect early disease or predict mortality. Prevention and treatment strategies focused on patients with microalbuminuria may definitively impact the burden of disease. This proposal will also study the effect of different anti-retroviral treatment regimens and clinical markers for the progression of HIV-infection such as plasma HIV RNA level or CD4 count on the progression of nephropathy. These effects will be explored using a retrospective cohort design among the patients with evidence of nephropathy identified in the cross-sectional survey and among patients enrolled in the Women's Interagency HIV Study. This information combined with our knowledge of renal pathophysiology and the progression of kidney diseases can then be used to design effective prevention and treatment strategies aimed at decreasing the morbidity and mortality associated with this devastating nephropathy.
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