Answer
The cellular target in the development of HIVAN is probably the renal glomerular and tubular epithelium. Using in situ hybridization and polymerase chain reaction assays to detect HIV-1 DNA and messenger ribonucleic acid (mRNA), investigators have shown that renal glomerular and tubular epithelial cells are productively infected by HIV-1 in patients with HIVAN; this argues strongly for localized replication of HIV-1 in the kidney and for the existence of a renal viral reservoir.
Further, circularized viral DNA, a marker of recent nuclear import of full-length, reverse-transcribed RNA, has been detected in kidney biopsy samples from patients with HIVAN, suggesting active replication in renal tissue. [6] However, the mechanisms of virus-induced renal injury remain undetermined.
Peculiar histopathologic features of HIVAN are the enhanced proliferation and the loss of differentiation markers of glomerular epithelial cells. In one study, HIV-1 infection was shown to kill renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas up-regulation, suggesting that apoptosis of nonlymphoid cells can be directly induced by HIV-1. The net and long-standing glomerular and tubular epithelial cell damage leads to proteinuria, glomerulosclerosis, and tubulointerstitial scarring.
The role of cytokines has not been established, and although their presence is not essential for the development of HIVAN, cytokines may modify the progression of infection or a patient's susceptibility to infection. The levels of cytokines are increased in renal biopsy samples from patients with HIVAN.
In one study, mesangial and tubular cell production of interleukin-6 and tumor necrosis factor–alpha was shown to be a potent stimulus for HIV-1 expression in HIV-1–infected monocytes. [7] Viral replication in response to cytokines may play an important role in the pathogenesis of HIVAN.
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Light microscopy with trichrome staining showing the collapse of the glomerular tuft, with segmental glomerular and interstitial sclerosis (bluish staining). The renal tubules are dilated and filled with proteinaceous material.
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Light microscopy showing prominent microcystic dilatation of renal tubules filled with proteinaceous material; this finding is characteristic of human immunodeficiency virus (HIV)–associated nephropathy, although it may also be observed in chronic glomerulonephritis.
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Electron microscopy showing a segment of the glomerular basement membrane; foot process effacement (black arrow) and prominent tubuloreticular inclusions (red arrow) are present.
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Types of electrolyte abnormalities observed with some of the drugs used to treat opportunistic infections in patients with human immunodeficiency virus (HIV). ARF stands for acute renal failure.
