A 20-year history of childhood HIV-associated nephropathy

Abstract

In 1984, physicians in New York and Miami reported HIV-infected adult patients with heavy proteinuria and rapid progression to end-stage renal disease. These patients showed large edematous kidneys with a combination of focal segmental glomerulosclerosis (FSGS) and tubulointerstitial lesions. This renal syndrome, named HIV-associated nephropathy (HIVAN), was found predominantly in African Americans. Subsequent studies confirmed the presence of HIVAN in children, who frequently develop nephrotic syndrome in association with FSGS and/or mesangial hyperplasia with microcystic tubular dilatation. Since then, substantial progress has been made in our understanding of the etiology and pathogenesis of HIVAN. This article reviews 20 years of research into the pathogenesis of HIVAN and discusses how these concepts could be applied to the treatment of children with HIVAN. HIV-1 infection plays a direct role in the pathogenesis of childhood HIVAN, at least partially by affecting the growth and differentiation of glomerular and tubular epithelial cells and enhancing the renal recruitment of infiltrating mononuclear cells and cytokines. An up-regulation of renal heparan sulfate proteoglycans seems to play a relevant role in this process, by increasing the recruitment of heparin-binding growth factors (i.e., FGF-2), chemokines, HIV-infected cells, and viral proteins (i.e., gp120, Tat). These changes enhance the infectivity of HIV-1 in the kidney and induce injury and proliferation of intrinsic renal cells. Highly active anti-retroviral therapy (HAART) appears to be the most promising treatment to prevent the progression of childhood HIVAN. Hopefully, in the near future, better education, prevention, and treatment programs will lead to the eradication of this fatal childhood disease.

Iron-Related Proteins

“…H IV-infected children can develop proteinuria secondary to several renal diseases, including immune complex glomerulopathies, thrombotic microangiopathies (TMA), and HIV-associated nephropathy (HIVAN) (1)(2)(3)(4)(5). In general, these renal diseases show a progressive clinical onset, and can have a significant clinical impact in the quality of life of HIV-infected children.…”

“…Childhood HIVAN is typically seen in African American patients and is defined by the presence of heavy proteinuria, with mesangial hyperplasia or focal segmental glomerulosclerosis (FSGS) in association with microcystic tubular changes, leading to renal enlargement and rapid progression of the renal disease (1)(2)(3)(4)(5). HIV-infected children can also develop an atypical form of the Hemolytic Uremic Syndrome (HUS) characterized by a progressive clinical onset, lack of preceding diarrhea, preserved urine output with severe proteinuria, and rapid progression to end-stage renal disease or death due to infectious or bleeding complications (3,4,9).…”

Human Immunodeficiency Virus-Associated Nephropathy (HIVAN) in Indian Children

“…There are very few reports about HIV-associated nephropathy in children [4]. This is the first report from India.…”

“…Several mechanisms for pathogenesis have been implicated. HIV-1 virus may directly affect the growth and differentiation of glomerular and tubular epithelial cells, increase recruitment of infiltrating mononuclear cells and cytokines, and upregulate renal heparin sulphate proteoglycans [1,4]. Other agents that can lead to associated renal disease are opportunistic infections, nephrotoxic agents and immunological abnormalities [5].…”

Genetic Susceptibility, HIV Infection, and the Kidney

“…The association between HIV and renal disease was first reported in 1984, shortly after the discovery of HIV (44). In the first 10 yr of the AIDS epidemic, the increase in the incidence of ESRD as a result of HIVAN surpassed any other cause of kidney disease.…”