Miscellaneous HIV-associated Renal Diseases

Miscellaneous HIV-associated Renal Diseases

A. Brad Farris, III, MD

Lupus-like GN is one of the more frequent diseases associated with HIV, typically showing a markedly expanded mesangium image, thickened capillary walls image, and inflammatory cells in glomerular capillary loops image.

Fibrillary GN is one glomerular disease associated with HIV infection. Fibrils image are evident in the GBM in an electron micrograph from a 50-year-old HIV(+), HCV(+) man with 11 g/d proteinuria. Congo red stain was (-).



  • HIV-associated renal diseases (HIV-ARD)


  • Renal diseases other than collapsing glomerulopathy (HIVAN) that occur particularly in patients infected with HIV, due to direct effect on kidney, altered immune system, or drug toxicity



  • Chronic immune complex disease in HIV-infected patients that has LM, IF, and EM features of lupus nephritis, but patients have no other evidence of lupus nephritis

  • Described by Haas et al and Nochy et al


  • Probably related to immune dysregulation

  • Loss of CD4(+) T regulatory cells causes autoimmune disease

  • Role of infectious agent not excluded


  • Possibly 2nd most common form of glomerular lesions (after HIVAN) in HIV patients undergoing biopsy

  • Many (13/14 in the Haas Baltimore study) were African-American

  • Nochy’s study in Europe showed equal proportions of whites and blacks having lupus-like GN

  • In series of > 100 biopsies for glomerular disease in HIV(+) patients, 3% had lupus-like GN


  • Hematuria and proteinuria/nephrotic syndrome

  • Share other features such as anemia, leukopenia, multiorgan involvement, and serositis

Laboratory Tests

  • ± ANA and anti-double-stranded (ds) DNA and ↓ complements

    • Assessment somewhat complicated because some HIV patients have low-titer ANAs

      • Screening of > 150 patients with AIDS found 19 to be ANA(+) but only 2 at high titer and none anti-dsDNA Ab(+)


  • Corticosteroids, ACE inhibitors, highly active antiretroviral therapy (HAART) have all been used


  • Outcome can be poor, because many patients present with advanced disease

Microscopic Pathology

  • Focal/diffuse proliferative GN or membranous nephropathy


  • “Full house” pattern of IgG, IgA, IgM, C3, and C1q

Electron Microscopy

  • Essentially all have tubuloreticular inclusions

  • Most common pattern appears to be combination of mesangial, subendothelial, subepithelial, and intramembranous deposits

Differential Diagnosis

  • Lupus nephritis

    • HIV-associated lupus-like GN lacks positive lupus serologies (ANA, dsDNA) and nonrenal manifestations

    • “Full house” immunofluorescence staining pattern is more commonly seen in lupus than in HIVAN

    • Tubuloreticular inclusions may be seen in both lupus nephritis and HIVAN



  • IgA(+) glomerular disease arising in HIV(+) patients that has clinical and pathologic aspects similar to idiopathic IgA nephropathy

  • Reports have also included Henoch-Schönlein purpura with nephritis


  • Deposits eluted from glomeruli have shown specificity for HIV envelope (e.g., gp41, gp120, gp160) or core proteins (e.g., p24) (Kimmel et al)


  • Series (many of which are from Europe) indicate higher incidence of IgA nephropathy in white patients with HIV infection

  • Data conflicts regarding prevalence of IgA deposits in patients dying from AIDS

    • Some series indicate high prevalence of IgA deposits in AIDS patients, but this does not necessarily correlate with increased IgA nephropathy rate


  • Hematuria and low-grade proteinuria are common

  • May present with Henoch-Schönlein purpura (HSP)-type picture (rash [leukocytoclastic angiitis of the skin], etc.)

Laboratory Tests

  • Associated with IgA-containing cryoglobulins

  • ↑ IgA levels, IgA-containing circulating immune complexes, and IgA-rheumatoid factor


  • ACE inhibitors may be useful


  • Thought to be same as IgA nephropathy in non-HIV-infected patients

Microscopic Pathology

  • Does not differ drastically from conventional IgA nephropathy seen in absence of HIV

    • Mesangial proliferation ± collapsing glomerulosclerosis (coexisting HIVAN)


  • Shows mesangial IgA deposits like conventional IgA nephropathy seen in absence of HIV

Electron Microscopy

  • In contrast with idiopathic IgA nephropathy, there are also numerous tubuloreticular structures that provide a clue to presence of HIV



  • TMA associated with HIV infection

  • Both syndromes resembling thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) can occur in HIV-infected patients


  • Etiology not known

    • HIV injury to endothelium or infection of megakaryocytes may be involved

    • Escherichia coli 0157:H7 appears not to be involved

    • Appears that ADAMTS13 level is not ↓ in HIV-associated TMA as it is in TTP

    • Etiology role has been attributed to CMV infection, cryptosporidiosis, AIDS-related neoplasia, drugs, and antiphospholipid antibodies


  • Human data are lacking

    • Multicenter autopsy study showed 15 of 214 patients (7%) with deaths attributable to AIDS had evidence of TMA

    • French study (Peraldi et al) attributed rapid decline in renal function to HUS-type syndrome in 32 of 92 patients

    • 6/27 (22.2%) pigtailed macaques (Macaca nemestrina) acutely infected with HIV-2 developed histological and EM features of renal TMA such as glomerular capillary platelet thrombi and mesangiolysis


  • Acute renal failure ± proteinuria and hematuria

  • Microangiopathic hemolytic anemia and thrombocytopenia

  • Presentations may be classified as either HUS or TTP (neurologic symptoms and fever)

Laboratory Tests

  • ± thrombocytopenia ± schistocytosis


  • Treatment of underlying HIV may be best approach

  • Plasmapheresis and fresh frozen plasma have been used

  • Rituximab and corticosteroids have been used

  • Hemodialysis may be needed at presentation


  • High mortality: More severe in HIV-infected patients than in non-HIV-infected patients

Microscopic Pathology

  • Pathologic findings are similar to those of TMA in non-HIV-infected patients

    • Mucoid arterial intimal hyperplasia and intraluminal thrombi may be observed

    • Fragmented intramural RBCs in vessels

  • May coexist with HIVAN

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Miscellaneous HIV-associated Renal Diseases

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