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. HIV-associated nephropathy (HIVAN) is the most common cause of end-stage renal failure seen in HIV-1 seropositive patients of African descent and the fourth leading cause of death in HIV+ individuals. It is estimated that up to 30% of black HIV+ patients will develop HIVAN. Untreated HIV+ individuals with HIVAN progress rapidly to end-stage renal disease (ESRD) within 6-12 months. The pathogenesis of the disease is unknown and definitive diagnosis of HIVAN involves a kidney biopsy. We have preliminary data detecting HIV proteins in vesicles from urine of HIVAN and HIV+ patients using mass spectrometry. This is the first report of detecting HIV proteins in urine and we have a provisional patent for these findings. We hypothesize that these HIV urinary proteins will serve as unique biomarkers to detect HIVAN disease and/or HIV disease progression. Biomarkers hold much potential as a clinical diagnostic tool, but they must be validated, quantified and statistically associated with a specific disease. We propose to do this by the following specific aim: To associate the presence of specific HIV proteins with HIVAN disease and/or HIV disease progression. Our research group has identified 12 different HIV proteins in urinary vesicles using mass spectrometry methods. We will validate and quantify these proteins using isobaric tags for relative and absolute quantification (iTRAQ) methods and develop a multiplex bead analysis to more quickly detect and quantitate these proteins. These results will be statistically analyzed for associations and correlations to HIVAN and HIV disease progression. We propose to use the data generated from this project for submission of a full patent. We envision this patent eventually to evolve into a rapid HIV test such as the pregnancy sticks that could be used in resource poor areas of the world to more quickly diagnose HIV infection and disease progression.
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