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Controversies in the pathogenesis of HIV-associated renal diseases

Nature Reviews Nephrology volume 5, pages 574–581 (2009)Cite this article

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

  • HIV-associated nephropathy (HIVAN) and HIV immune-complex kidney disease (HIVICK) are the most common renal diseases in patients with HIV-1

  • 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

  • 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

  • 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

  • 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

  • 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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Figure 1: Renal biopsy sample from a patient with HIV-associated nephropathy.
Figure 2: The interplay of environmental (red) and genetic (blue) factors in 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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  1. Department of Medicine and Rammelkamp Center for Education and Research, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Leslie A. Bruggeman

  2. Division of Nephrology, University of Washington, Seattle, WA, USA

    Peter J. Nelson

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Correspondence to Leslie A. Bruggeman.

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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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