Pathogenesis and Treatment of HIV-Associated Renal Diseases: Lessons from Clinical and Animal Studies, Molecular Pathologic Correlations, and Genetic Investigations

  1. Moderator: Paul L. Kimmel, MD;
  2. Discussants: Laura Barisoni, MD; and
  3. Jeffrey B. Kopp, MD
  1. From George Washington University Medical Center, Washington, DC, and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
    1. Figure 1. . Data obtained from the Centers for Disease Control and Prevention. Reproduced with permission from reference 27, Kidney Int. 2003; 63:1618-31.
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      Figure 1. . Data obtained from the Centers for Disease Control and Prevention. Reproduced with permission from reference 27, Kidney Int. 2003; 63:1618-31. Percentage of HIV-infected patients receiving hemodialysis in the U.S. hemodialysis program
    2. Figure 2. . Interferon-α protein was assessed in microdissected renal glomerular and interstitial tissue from 6 patients with HIV-associated nephropathy, 4 patients with HIV-associated immune-mediated glomerulonephritis, 3 HIV-infected patients who died without autopsy evidence of renal disease, 9 patients with idiopathic focal segmental glomerulosclerosis in the absence of HIV infection, and renal tissue of uninfected patients without clinical or pathologic evidence of renal disease by high-performance immunoaffinity chromatography and chemiluminescent enzyme-linked immunosorbent assay. Renal interstitial and glomerular interferon-α protein levels were significantly higher in renal tissue from patients with HIV-associated nephropathy than in tissue from all other groups ( = 0.002; analysis of variance). A similar pattern was noted for nonpolymorphic major histocompatibility II locus and interferon-γ receptor protein levels. Error bars indicate SEs. * = 0.002.
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      Figure 2. . Interferon-α protein was assessed in microdissected renal glomerular and interstitial tissue from 6 patients with HIV-associated nephropathy, 4 patients with HIV-associated immune-mediated glomerulonephritis, 3 HIV-infected patients who died without autopsy evidence of renal disease, 9 patients with idiopathic focal segmental glomerulosclerosis in the absence of HIV infection, and renal tissue of uninfected patients without clinical or pathologic evidence of renal disease by high-performance immunoaffinity chromatography and chemiluminescent enzyme-linked immunosorbent assay. Renal interstitial and glomerular interferon-α protein levels were significantly higher in renal tissue from patients with HIV-associated nephropathy than in tissue from all other groups ( = 0.002; analysis of variance). A similar pattern was noted for nonpolymorphic major histocompatibility II locus and interferon-γ receptor protein levels. Error bars indicate SEs. * = 0.002. Interferon-α protein expression in renal tissue compartmentsPP
    3. Figure 3. Human HIV-associated nephropathy: A glomerulus shows global collapse of capillary lumina. The glomerular basement membranes are wrinkled and folded, and the urinary space is occupied by proliferating podocytes forming pseudocrescents. Numerous protein reabsorption droplets are present in the podocyte cytoplasm, and this cytoplasm is more abundant than normal (silver staining; original magnification, ×60). Tubulointerstitial damage includes interstitial fibrosis with inflammation, tubular atrophy, and microcysts. Eosinophilic casts are present in the dilated tubular lumina (silver staining; original magnification, ×40). Ultrastructural analysis shows a collapsed glomerular capillary. Note the wrinkling of the glomerular basement membrane. Podocytes ( ) have lost foot processes and primary processes, and their cell body sits directly on the glomerular basement membrane. There is focal detachment of podocytes from the underlying glomerular basement membrane and new matrix deposition ( ). (Original magnification, ×8000.) Membrane nephropathy in HIV-1 transgenic mice: Immunostaining for synaptopodin in wild-type ( ) and HIV-1 transgenic mice ( ): All the glomeruli are stained for synaptopodin in kidneys from wild type ( ). No staining is noted in the kidney of the HIV-1 transgenic mice ( ). (Original magnification, ×20.) Immunostaining for adducin ( ) and Na , K –adenosine triphosphatase ( ) in HIV-1 transgenic mice: No basolateral staining is noted in this dilated tubule, whereas the nondilated tubules display a delicate basolateral staining ( ). (Original magnification, ×40.).
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      Figure 3. Human HIV-associated nephropathy: A glomerulus shows global collapse of capillary lumina. The glomerular basement membranes are wrinkled and folded, and the urinary space is occupied by proliferating podocytes forming pseudocrescents. Numerous protein reabsorption droplets are present in the podocyte cytoplasm, and this cytoplasm is more abundant than normal (silver staining; original magnification, ×60). Tubulointerstitial damage includes interstitial fibrosis with inflammation, tubular atrophy, and microcysts. Eosinophilic casts are present in the dilated tubular lumina (silver staining; original magnification, ×40). Ultrastructural analysis shows a collapsed glomerular capillary. Note the wrinkling of the glomerular basement membrane. Podocytes ( ) have lost foot processes and primary processes, and their cell body sits directly on the glomerular basement membrane. There is focal detachment of podocytes from the underlying glomerular basement membrane and new matrix deposition ( ). (Original magnification, ×8000.) Membrane nephropathy in HIV-1 transgenic mice: Immunostaining for synaptopodin in wild-type ( ) and HIV-1 transgenic mice ( ): All the glomeruli are stained for synaptopodin in kidneys from wild type ( ). No staining is noted in the kidney of the HIV-1 transgenic mice ( ). (Original magnification, ×20.) Immunostaining for adducin ( ) and Na , K –adenosine triphosphatase ( ) in HIV-1 transgenic mice: No basolateral staining is noted in this dilated tubule, whereas the nondilated tubules display a delicate basolateral staining ( ). (Original magnification, ×40.). Histopathologic characteristics of HIV-associated nephropathy in humans and transgenic mice.A.B.C.PasterisksD and E.DEDEF and G.F++Gbrown
    4. Figure 4. .
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      Figure 4. . Model for glomerular and tubular cell injury induced by HIV-1
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    1. Ann Intern Med August 5, 2003 vol. 139 no. 3 214-226
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