Abstract
The two most common HIV-associated renal diseases, HIV-associated nephropathy and HIV immune-complex kidney disease, share the common pathologic finding of hyperplasia within the glomerulus. Podocyte injury is central to the pathogenesis of these diseases; however, the source of the proliferating glomerular epithelial cell remains a topic of debate. Parenchymal injury has been linked to direct infection of renal epithelial cells by HIV-1, although the mechanism of viral entry into this non-lymphoid compartment is unclear. Although transgenic rodent models have provided insight into viral proteins responsible for inducing renal disease, such models have substantial limitations. Rodent HIV-1 models, for instance, cannot replicate all features of immune activation, a process that could have an important role in the pathogenesis of the HIV-associated renal diseases.
Key Points
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HIV-associated nephropathy (HIVAN) and HIV immune-complex kidney disease (HIVICK) are the most common renal diseases in patients with HIV-1
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HIVAN seems to be caused directly by HIV-1 infection, possibly via disruption of normal homeostatic functions of mature podocytes caused by HIV proteins Nef, Vpr and Tat
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Contrary to HIVAN, HIVICK is not observed in rodent models of HIV-1, which might mean that virus replication or immune response to viral proteins—not expression of viral genes alone—induce this condition
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The mechanism by which renal parenchymal cells are infected by HIV-1 does not seem to involve the same CD4–chemokine co-receptor mechanism that the virus uses to infect immune cells
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Hyperplastic injury in the glomerulus is a common pathogenic event of the HIV-associated renal diseases, although the source of the proliferative epithelial cell is unclear
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Immune activation, both systemic and within the kidney, is dramatically altered in HIV-1 infection and might have a role in precipitating and exacerbating HIV-associated renal diseases
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Acknowledgements
Dr. Bruggeman is supported by NIH grants DK061395 and DK077668 and is a member of the Case Center for AIDS Research supported by NIH grant AI36219. Dr. Nelson is supported by NIH grants DK065498, DK079498, and DK083375.
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Bruggeman, L., Nelson, P. Controversies in the pathogenesis of HIV-associated renal diseases. Nat Rev Nephrol 5, 574–581 (2009). https://doi.org/10.1038/nrneph.2009.139
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DOI: https://doi.org/10.1038/nrneph.2009.139
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