HIVAssociated Nephropathy

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HIV-Associated Nephropathy

• Saleem Bharmal
• 9/23/08

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HIV-Associated Nephropathy

• Association between HIV and renal disease first
  reported in 1984
• HIV-1 seropositive patients
• Renal syndrome characterized by progressive renal
  failure and proteinuria
• Most common kidney biopsy finding was FSGS

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HIV-Associated Nephropathy

• HIV-1 seropositive
• Low CD4 counts (lt 250) and/or other criteria for
  AIDS
• Proteinuria, often in the nephrotic range
• Most patients have moderate to severe renal
  insufficiency at the time of diagnosis
• Peripheral edema is uncommon
• Hypertension is rare
• Renal ultrasound shows echogenic kidneys that are
  normal-to-large in size

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Key Histopathologic Features

• Collapsing form of Focal segmental
  glomerulosclerosis (FSGS)
• Microcystic dilatation or renal tubules
• Globally sclerotic glomeruli
• Lymphocytic interstitial infiltrates and
  Interstitial fibrosis
• Podocyte proliferation and loss of podocyte
  differentiation markers
• Endothelial tubuloreticular inclusions seen on EM

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Collapsing FGS and Microcystic Dilatation of the
Tubules
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Endothelial Tubuloreticular Inclusions (TRI)
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Role of Biopsy

• Only 40-50 are confirmed to be HIVAN by renal
  biopsy in suspected cases
• Alternative findings include
• MPGN (Hep C) MN (Hep B)
• IgA nephropathy Diabetic nephropathy
• Amyloidosis AIN
• Cryoglobulinemia MCD

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Racial Predilection and Genetic Factors

• Effects mainly black and hispanic patients
• In the US, black patients with HIV-1 are 12 times
  more likely to develop HIVAN than non-black
  patients.
• Now the third leading cause of ESRD in African
  Americans between age 20 and 64
• Marked racial disparity suggests genetic factors
  are important determinants of HIVAN

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HIV-1 transgenic mouse model

• Mice transgenic for replication defective HIV-1
  construct lacking gag/pol genes developed
  proteinuria, renal failure, and histologic
  disease identical to HIVAN
• Nephropathy developed in kidney transplanted from
  transgenic mice into wild type, but not in
  kidneys from normal wild type transplanted into
  transgenic mice

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Confirmation that HIV-1 infects Renal Epithelial
Cells

• Bruggeman et al. reported a series of 20 HIV-1
  seropostive pts with renal disease who underwent
  renal biopsy
• 15 of the 20 pts had HIVAN confirmed by biopsy
• In 11 of the 15 pts with HIVAN, HIV-1 was
  detectable in renal epithelial cells by RNA in
  situ hybridization
• HIV-1 RNA was detected in renal tubular
  epithelial cells, glomerular visceral and
  parietal epithelial cells, and interstitial
  leukocytes

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Reservoir for HIV-1

• Bruggeman et al. later detected HIV-1in renal
  cells by both RNA in situ hybridization and DNA
  in situ PCR in 3 patients with undetectable viral
  loads
• Case repot by Winston et al. described a pt who
  developed HIVAN with acute HIV-1 seroconversion
  that imporved with HAART however the pt continued
  to express HIV-1 in renal epithelial cells

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HIV-1 Genome

• Consists of 9 genes that encode fifteen protein

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Podocytes

• Podocytes are normally terminally differentiated,
  quiescent cells that do not proliferate
• The collapsing glomerulopathy of HIVAN is
  characterized by marked podocyte
  dedifferentiation and proliferation
• Husain et al. showed that nef in vitro is
  necessary to cause most of the podocyte changes
  seen in HIVAN

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Treatments (HAART)
HIV-1-associated nephropathy incidence stratified
by AIDS status and antiretroviral use. White
bars, no antiretroviral therapy light grey bars,
nucleoside reverse transcriptase inhibitor
therapy dark gray bars, highly active
antiretroviral therapy.
The incidence of HIV-1-associated nephropathy by
calendar period and AIDS status.
Lucas AIDS, Volume 18(3).February 20,
2004.541-546
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Treatments

• ACE Inhibitors Small studies have shown benefit
  in patients who have been put on ACEI complared
  to those who were not on ACEI with decrease in
  proteinuria and decrease rate of renal
  dysfunction
• ? Prednisone Only a few small retrospective
  cohort studies have shown decrease in serum Cre
  and prtoeinuria after treatment with prednisone