Mechanisms of Proteinuria in HIV.

Journal Article (Journal Article;Review)

Proteinuria is common in the setting of HIV infection, and may reflect comorbid kidney disease, treatment-related nephrotoxicity, and HIV-related glomerular diseases. The mechanisms of podocyte and tubulointerstial injury in HIV-associated nephropathy (HIVAN) have been the subject of intense investigation over the past four decades. The pathologic contributions of viral gene expression, dysregulated innate immune signaling, and ancestry-driven genetic risk modifiers have been explored in sophisticated cellular and whole animal models of disease. These studies provide evidence that injury-induced podocyte dedifferentiation, hyperplasia, cytoskeletal dysregulation, and apoptosis may cause the loss of glomerular filtration barrier integrity and slit diaphragm performance that facilitates proteinuria and tuft collapse in HIVAN. Although the incidence of HIVAN has declined with the introduction of antiretroviral therapy, the collapsing FSGS lesion has been observed in the context of other viral infections and chronic autoimmune disorders, and with the use of interferon-based therapies in genetically susceptible populations. This highlights the fact that the lesion is not specific to HIVAN and that the role of the immune system in aggravating podocyte injury warrants further exploration. This review will summarize our progress in characterizing the molecular mechanisms of podocyte dysfunction in HIVAN and other forms of HIV-associated kidney disease.

Full Text

Duke Authors

Cited Authors

  • Hall, G; Wyatt, CM

Published Date

  • 2021

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 749061 -

PubMed ID

  • 34722586

Pubmed Central ID

  • PMC8548571

International Standard Serial Number (ISSN)

  • 2296-858X

Digital Object Identifier (DOI)

  • 10.3389/fmed.2021.749061


  • eng

Conference Location

  • Switzerland