Tuesday, September 13, 2011

In The News:- HIV Nephropathy and other adverse risk factors

Incidence of HIV-associated has been decreased significantly after advent of HAART. We hypothesized that patients who has sustained podocyte HIV expression before the start of HAART are vulnerable to develop HIV-associated nephropathy during the development of adverse host factors such as the activation of renin-angiotensin-sytem (because of the development of diabetes or loss of critical nephron mass as a result of nephrotoxic drugs or trauma etc) , despite having undetectable viral load. Since HIV patients are now living almost a normal life and are prone to develop diabetes and hypertension, they are likely to develop the activation of the RAS in their later life. To test our hypothesis,  HIV transgenic Vpr mice (which display doxycycline [Doxy] specific podocyte Vpr expression) with 2, 3, and 4 angiotensinogen (Agt) copies (Vpr-Agt-2, Vpr-Agt-3, and Vpr-Agt-4) were administered Doxy for 3 weeks to manifest clinically occult (in situ) HIVAN followed by Doxy-free water during the next 3 weeks. Subsequently, renal biomarkers were collected and kidneys were harvested for renal histology. Vpr mice with Agt copies did not develop proteinuria and blood pressure, and displayed minimal glomerular and tubular lesions only, without any microcyst formation. Vpr mice with 3 Agt copies showed mild glomeular and tubular lesions and microcyst formation; whereas, Vp mice 4 Agt copies exhibited moderate proteinuria, hypertension, glomerular sclerosis, tubular dilatation, microcysts and expression of epithelial mesenchymal transition markers. Moreover, Vpr mice 4 Agt copies displayed enhanced renal tissue expression of Agt, renin, and ACE and also showed higher (P<0.04) renal tissue concentration of Ang II. In addition, renal cells in Vpr mice 4 Agt copies showed enhanced expression of TGF-β, connective tissue growth factor, and vascular endothelial growth factor (VEGF). These findings indicate that adverse host factors such as the activation of the RAS, promotes the progression of clinically occult HIVAN to overt HIVAN despite the absence of active viral activity. Thus, to prevent HIVAN early detection of HIV infection (prior to renal cell infection) and treatment would be important. 

Post by Pravin Singhal, MD

Dr. Singhal is a NIH funded investigator in the Division of Kidney Diseases and Hypertension at the Hofstra NSLIJ School of Medicine, NY

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