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HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment

Key Points

  • Widespread use of antiretroviral therapy has led to a change in the spectrum of renal pathologies associated with HIV infection

  • The incidence of HIV-associated nephropathy (HIVAN) has decreased since the introduction of combined antiretroviral therapy (cART)

  • Viral factors that likely contribute to renal injury in HIV-positive patients include direct infection of podocytes and renal tubular epithelial cells as well as the HIV proteins Nef and Vpr

  • APOL1 genetic variants predispose to HIVAN but not to HIV-immune-complex kidney disease

  • All HIV-positive individuals should undergo periodic (at least annual) screening of renal function

  • All patients with HIV-associated kidney diseases should receive cART; standard therapies for chronic kidney disease are also recommended

Abstract

HIV is a highly adaptive, rapidly evolving virus, which is associated with renal diseases including collapsing glomerulopathy—the classic histomorphological form of HIV-associated nephropathy. Other nephropathies related to viral factors include HIV-immune-complex kidney disease and thrombotic microangiopathy. The distribution of HIV-associated kidney diseases has changed over time and continues to vary across geographic regions worldwide. The reasons for this diversity are complex and include a critical role of APOL1 variants and possibly other genetic factors, disparities in access to effective antiviral therapies, and likely other factors that we do not yet fully understand. The mechanisms responsible for HIVAN, including HIV infection of podocytes and tubular epithelial cells, the molecules responsible for HIV entry, and diverse mechanisms of cell injury, have been the focus of much study. Although combined antiretroviral therapy is effective at preventing and reversing HIVAN, focal segmental glomerulosclerosis, arterionephrosclerosis and diabetic nephropathy are increasingly common in individuals who have received such therapy for many years. These diseases are associated with metabolic syndrome, obesity and premature ageing. Future directions for HIV-related kidney disease will involve regular screening for drug nephrotoxicity and incipient renal disease, as well as further research into the mechanisms by which chronic inflammation can lead to glomerular disease.

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Figure 1: Prevalence of HIV infection in adults in 2009.
Figure 2: Mechanisms of collapsing glomerulopathy in HIVAN.

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Acknowledgements

The authors' work is supported in part by the Intramural Research Programs of the National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, and National Institutes of Health, USA, and by the Medical Research Council and National Research Foundation of South Africa. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. Content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, USA, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The authors note with regret the recent untimely death of Linda Kao, a pioneering and generous researcher who made many important contributions to the field of human genetics, in particular to the discovery of the chromosome 22 locus that includes APOL1 as a risk factor for HIVAN.

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Correspondence to Jeffrey B. Kopp.

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Rosenberg, A., Naicker, S., Winkler, C. et al. HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment. Nat Rev Nephrol 11, 150–160 (2015). https://doi.org/10.1038/nrneph.2015.9

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