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) affects predominantly HIV + individuals of African descent and is the third leading cause of end stage renal disease in African Americans (AA). The relative risk for HIVAN is 18 times higher for AA than other races. After diagnosis of HIVAN, patients can quickly progress to end stage renal failure in six to nine months with the development of focal segmental glomerulosclerosis (FSGS). The increased occurrence of HIVAN in AA prompted us to examine genetic factors that could be involved in predisposition to disease. We hypothesized that HIV infection acts as a catalyst in patients predisposed to renal disease and accelerates progression to end stage renal disease (ESRD). We are determining if specific polymorphisms in genes contributing to increased ET-1 production are common in HIVAN patients. Polymorphisms in the ET-1, ECE-1, and angiotensin converting enzyme I (ACE I) genes will be examined in patient genomic DNA. The polymorphisms will be correlated to the patients' plasma ET-1 levels and induction of ET-1, ECE-1 and ACE I mRNA in cultured macrophages. In addition, we are identifying specific circulating inflammatory mediators involved in HIVAN disease. The presence of inflammatory mediators that enhance ET-1 induction will be quantified in plasma, urine and cultured macrophages and statistically compared between the patient groups. We hope to identify a profile of factors that are associated specifically with HIVAN.
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