HIV-associated Collapsing Glomerulopathy

HIV-associated Collapsing Glomerulopathy

A. Brad Farris, III, MD

Classic appearance of HIVAN with glomerular collapse image and proliferation of overlying podocytes image is well demonstrated by PAS stains in this HIV(+) man. The podocyte hypercellularity mimics a crescent.

Tubuloreticular inclusions (TRIs) image are almost always detectable in the endothelium in HIVAN, in contrast to idiopathic collapsing glomerulopathy. This sample is from an HIV(+) black man with 29 g/d proteinuria.



  • HIV-associated nephropathy (HIVAN)

  • HIV-associated collapsing glomerulopathy


  • Characteristic renal disease developing in setting of HIV infection


Infectious Agents

  • HIV

    • Some suggest kidney is “reservoir” for HIV

      • HIV genome demonstrated in glomerular visceral and tubular epithelial cells in HIVAN

    • Abnormal maturation and differentiation of podocytes demonstrated (Barisoni et al)

    • Cytokines may have role

      • Abnormalities shown in transforming growth factor-β (TGF-β), basic fibroblast growth factor (bFGF), interleukin, and others

  • AIDS not required for condition to occur

Genetic Factors

  • Higher risk with African ancestry (except Ethiopian)

  • APOL1 polymorphism associated with HIVAN

Animal Models

  • Mice transgenic for HIV regulatory genes develop collapsing glomerulopathy

    • Renal HIV gene expression necessary for transgenic HIVAN

      • Normal kidneys fail to develop nephropathy when transplanted into HIV transgenic mice

      • Transplantation of transgenic kidneys into nontransgenic litter mates shows the renal HIVAN phenotype



  • Incidence

    • Average incidence of acute kidney injury is 2.7 episodes per 100 person-years

      • Higher within 1st 3 months of disease recognition: 19.3 episodes per 100 person-years

  • Gender

    • Majority (˜ 70%) male, particularly according to original descriptions

  • Ethnicity

    • Historically, up to 90% of African American blacks

    • Rare in whites


  • Proteinuria, nephrotic range

    • Severe, averaging 6-7 g/d

    • Edema, hypoalbuminemia, and hypercholesterolemia (nephrotic syndrome) uncommon

  • Renal dysfunction

    • Creatinine at diagnosis typically ˜ 5 mg/dL

  • Hypertension

    • Uncommon (in < 50%)

  • Microhematuria

Laboratory Tests

  • CD4 count does not correlate with HIVAN development

  • Hypercholesterolemia uncommon, possibly due to ↓ hepatic lipoprotein synthesis in AIDS patients


  • Drugs

    • Highly active antiretroviral therapy (HAART)

      • May reverse tubular microcysts and slow HIVAN progression

      • HAART reduction in viral load can ↑ renal survival

    • Angiotensin-converting enzyme (ACE) inhibitors

      • May slow HIVAN progression

  • Hemodialysis

  • Renal transplantation


  • Rapidly progressive, with ESRD often developing within months in most

    • Early in AIDS epidemic, mean time to dialysis < 2 months and median survival time of renal disease to death is 4.5 months


Ultrasonographic Findings

  • Enlarged, highly echogenic kidneys


General Features

  • Pale cortex

  • 0.5-1.0 mm cysts in cortex or at corticomedullary junction


  • Enlarged, mean combined weight up to 500 g in adults

  • 1.2-1.3x normal weight in children


Histologic Features

  • Glomeruli

    • Collapsing glomerulopathy

      • Capillary loops globally or segmentally collapsed without corresponding mesangial matrix ↑

      • Shrunken down, global glomerulosclerosis (GS) ± cystic Bowman space dilatation, which contains proteinaceous material

      • ± marked podocyte hyperplasia, protein resorption droplets, and mitoses (contrary to prior thought that podocytes could not undergo mitosis)

      • ± enlarged glomeruli

      • Global GS reduces glomerulus to acellular sclerotic ball

    • Podocytes prominent

      • May simulate a crescent

      • Starts with hypertrophy and hyperplasia of visceral epithelial cells

  • Tubules

    • Microcystic tubular dilatation (30-40% of cases)

      • ± scalloped tubular outline

      • ± PAS(+) proteinaceous casts (fuchsin[+] on trichrome) in renal tubules

      • Autopsy studies have shown near-complete replacement of renal cortical parenchyma by microcysts

    • Patchy epithelial injury, regeneration, degeneration, and necrosis, and eventual tubular atrophy

      • Flattened tubular epithelium and mitotic figures

      • Tubular resorption droplets prominent

  • Interstitium

    • Interstitial inflammation and edema

      • Mononuclear cells (including lymphocytes and monocytes) and plasma cells

    • Interstitial fibrosis typically present

  • Vessels

    • Typically unremarkable

    • Rare cases of thrombotic microangiopathy



  • Segmental IgM, C3, and C1q

    • ± IgM and C3 granular positivity

    • Resorption droplets in podocytes and proximal tubules stain for multiple plasma proteins

  • Prominent immune complex deposit would be indicative of additional diagnosis

    • Hepatitis C virus (HCV), lupus-like GN, IgA nephropathy can all be seen in HIV

Electron Microscopy

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on HIV-associated Collapsing Glomerulopathy

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