Renal and cardiovascular diseases in HIV-infected patients are increasingly reported and may be interrelated. Total proteinuria, a widely used initial screening marker for renal disease, is extremely common in HIV-infected patients. In the general population, proteinuria is also associated with systemic endothelial dysfunction, a predictor of future cardiovascular events. Therefore, we hypothesize that endothelial dysfunction may be associated with the high prevalence of proteinuria in the HIV-infected population. Furthermore, because protease inhibitors are associated with endothelial dysfunction, we hypothesize that this class of antiretrovirals may specifically result in glomerular endothelial disease, manifested initially as microalbuminuria.
The specific aims of this study are to (1) determine the relationships between proteinuria and systemic endothelial dysfunction in HIV-infected patients and (2) determine the effects of protease inhibitor-based HAART on microalbuminuria in HIV-infected patients. To address Aim #1, we propose to perform a prospective, cohort study of HIV-infected subjects cared for at the Indiana University Medical Center. Specifically, ultrasound-measured flow mediated dilation of the brachial artery (a physiologic measurement of endothelial function), lipids, insulin and glucose levels, anthropometrics, lifestyle factors, and blood pressures of two HIV-infected groups (those with persistent proteinuria vs. those without proteinuria) will be compared at baseline and again in two years.
Aim #2 will be addressed by performing a secondary analysis of a metabolic substudy (chaired by the principal investigator's primary mentor) of AIDS Clinical Trials Group study 384, which compared the use of protease inhibitor-based regimens with nonnucleoside reverse transcriptase-based regimens for the initial antiretroviral treatment of HIV-infected patients. Archived urine samples obtained at regular intervals through the duration of this substudy will be used to measure microalbuminuria levels. Taken together, the results of these studies will form the basis for future prevention and therapeutic trials targeted at both renal and cardiovascular diseases in HIV-infected patients. The proposed research will foster the principal investigator's clinical research career development, as supervised by established independent investigators (primary mentor: Michael P. Dub6) in the fields of HIV metabolic and renal complications, renal vascular and glomerular pathology, and clinical trials design and implementation.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-J (M1))
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Scott, Jane
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Indiana University-Purdue University at Indianapolis
Internal Medicine/Medicine
Schools of Medicine
United States
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Gupta, Samir K; Shen, Changyu; Mather, Kieren J et al. (2011) Neither proteinuria nor albuminuria is associated with endothelial dysfunction in HIV-infected patients without diabetes or hypertension. J Infect Dis 204:1946-50
Gupta, Samir K; Johnson, Raymond M; Mather, Kieren J et al. (2010) Anti-inflammatory treatment with pentoxifylline improves HIV-related endothelial dysfunction: a pilot study. AIDS 24:1377-80
Dube, Michael P; Shen, Changyu; Mather, Kieren J et al. (2010) Relationship of body composition, metabolic status, antiretroviral use, and HIV disease factors to endothelial dysfunction in HIV-infected subjects. AIDS Res Hum Retroviruses 26:847-54
Gupta, Samir K; Komarow, Lauren; Gulick, Roy M et al. (2009) Proteinuria, creatinine clearance, and immune activation in antiretroviral-naive HIV-infected subjects. J Infect Dis 200:614-8
Gupta, Samir K; Smurzynski, Marlene; Franceschini, Nora et al. (2009) The effects of HIV type-1 viral suppression and non-viral factors on quantitative proteinuria in the highly active antiretroviral therapy era. Antivir Ther 14:543-9
Gupta, Samir K; Johnson, Raymond M; Saha, Chandan et al. (2008) Improvement in HIV-related endothelial dysfunction using the anti-inflammatory agent salsalate: a pilot study. AIDS 22:653-5
Wools-Kaloustian, Kara K; Gupta, Samir K (2008) Will there be an epidemic of HIV-related chronic kidney disease in sub-Saharan Africa? Too soon to tell. Kidney Int 74:845-7
Gupta, Samir K (2008) Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. AIDS Patient Care STDS 22:99-103
Kalayjian, Robert C; Franceschini, Nora; Gupta, Samir K et al. (2008) Suppression of HIV-1 replication by antiretroviral therapy improves renal function in persons with low CD4 cell counts and chronic kidney disease. AIDS 22:481-7
Gupta, Samir K; Mather, Kieren J; Agarwal, Rajiv et al. (2007) Proteinuria and endothelial dysfunction in stable HIV-infected patients. A pilot study. J Acquir Immune Defic Syndr 45:596-8

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