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Taking a hard look at the pathogenesis of childhood HIV-associated nephropathy

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Abstract

Childhood human immunodeficiency virus-associated nephropathy (HIVAN) is defined by the presence of proteinuria associated with mesangial hyperplasia and/or global-focal segmental glomerulosclerosis, in combination with the microcystic transformation of renal tubules. This review discusses the pathogenesis of childhood HIVAN and explores how the current pathological paradigm for HIVAN in adults can be applied to children. The Human Immunodeficiency Virus-1 (HIV-1) induces renal epithelial injury in African American children with a genetic susceptibility to develop HIVAN. The mechanism is not well understood, since renal epithelial cells harvested from children with HIVAN do not appear to be productively infected. Children with HIVAN show a renal up-regulation of heparan sulphate proteoglycans and a recruitment of circulating heparin-binding growth factors, chemokines, and mononuclear cells. Macrophages appear to establish a renal HIV-reservoir and transfer viral particles to renal epithelial cells. All of these changes seem to trigger an aberrant and persistent renal epithelial proliferative response. The paradigm that viral products produced by infected renal epithelial cells per se induce the proliferation of these cells is not supported by data available in children with HIVAN. More research is needed to elucidate how HIV-1 induces renal epithelial injury and proliferation in HIV-infected children.

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Acknowledgments

This study was supported in part by the National Institutes of Health grants: R01-HL55605, R01-DK049419, K12RR17613, R21-AT002278.

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  1. Division of Nephrology and Center for Molecular Physiology, Children’s Research Institute, Children’s National Medical Center, 111 Michigan Av NW, Room 5346, Washington, D.C., 20010, USA

    Patricio E. Ray

  2. Department of Pediatrics, The George Washington University, Washington, D.C., USA

    Patricio E. Ray

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Ray, P.E. Taking a hard look at the pathogenesis of childhood HIV-associated nephropathy. Pediatr Nephrol 24, 2109–2119 (2009). https://doi.org/10.1007/s00467-009-1155-4

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