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
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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