Kidney nontumor / medical renal

Vascular disease


Pauci-immune complex crescentic glomerulonephritis / ANCA associated vasculitis

Editorial Board Member: Nicole K. Andeen, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Ana Belén Larqué, M.D., Ph.D.

Last author update: 11 January 2021
Last staff update: 11 January 2021

Copyright: 2019-2024,, Inc.

PubMed Search: ANCA related glomerulonephritis

Ana Belén Larqué, M.D., Ph.D.
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Cite this page: Larqué A. Pauci-immune complex crescentic glomerulonephritis / ANCA associated vasculitis. website. Accessed May 19th, 2024.
Definition / general
  • Pauci-immune necrotizing crescentic glomerulonephritis related to or caused by antineutrophil cytoplasmic antibody (ANCA)
Essential features
  • Pauci-immune necrotizing crescentic glomerulonephritis (renal biopsy: gold standard)
  • Rapidly progressive glomerulonephritis with hematuria and proteinuria
  • Small vessel necrotizing vasculitis associated with ANCAs that can be renal limited or with systemic vasculitis: granulomatous with polyangiitis, microscopic polyangiitis, eosinophlic granulomatous with polyangiitis or renal limited vasculitis (J Am Soc Nephrol 2010;21:1628)
  • Pauci-immune glomerulonephritis
  • Pauci-immune crescentic glomerulonephritis
  • ANCA associated vasculitis
ICD coding
  • ICD10: NO1.7 - rapidly progressive nephritic syndrome with diffuse crescentic glomerulonephritis
  • Kidney glomeruli
  • ANCA is a primary pathogenic factor, mainly by augmenting leukocyte endothelial interactions (Mod Rheumatol 2010;20:54)
  • In vitro evidence:
    • ANCA IgG can activate cytokine primed neutrophils by interacting with myeloperoxidase (MPO) or PR3 at the surface of the cells
    • Endothelial injury by ANCA activated neutrophils and disruption of glomerular capillary walls
    • Alternative complement pathway activation by ANCA activated neutrophils (Nat Rev Rheumatol 2014;10:463)
Clinical features
  • Rapid deterioration of renal function
  • Oliguria, hematuria and proteinuria (usually nonnephrotic range)
  • Flu-like syndrome common at onset (fever, arthralgia, myalgia)
  • Signs of extrarenal vasculitis in ~ 75% (Mod Rheumatol 2010;20:54, Semin Arthritis Rheum 2005;35:95)
    • Microscopic polyangiitis: renal involvement (90%), lung usually affected, also skin, ear, nose, throat, musculoskeletal, nervous system, gastrointestinal
    • Granulomatosis with polyangiitis: kidney, upper airway and lung involvement in 90% of cases
    • Eosinophilic granulomatosis with polyangiitis: four phases - allergic, eosinophilic, vasculitic, postvasculitic (Colvin: Diagnostic Pathology - Kidney Diseases, 2nd Edition, 2015)
  • Rapidly progressive glomerulonephritis clinically
  • Pauci-immune crescentic glomerulonephritis pathologically
  • Positivity for ANCA (Clin Rheumatol 2017;36:1949)
  • Extrarenal clinical manifestations in systemic vasculitis
  • Positive ANCA test by indirect immunofluorescence plus enzyme linked immunosorbent assays in serum
    • Sensitivity of 80% and specificity of 96% for pauci-immune glomerulonephritis
    • Negative ANCA in ~ 20% of pauci-immune glomerulonephritis
  • Type of ANCA does not permit specific diagnosis
    • MPO ANCA most common in pauci-immune glomerulonephritis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (50 - 60%)
    • PR3 ANCA most common in granulomatosis with polyangiitis (~ 75%)
  • Other (atypical) ANCA specificities described
    • React with lactoferrin, elastase and P-cathepsin-G in serum
    • Found in variety of conditions with chronic inflammation or infection
  • Negative ANCA associated with absence of disease activity
  • Normal complement levels in serum
  • Peripheral eosinophilia in 10 - 20% of microscopic polyangiitis
  • References: Kidney Int 2000;57:846, Clin Rev Allergy Immunol 2013;45:109
Prognostic factors
  • ~ 75% achieve remission
  • ~ 30% relapse, frequently with PR3 ANCA
  • 60 - 75% 5 year patient and kidney survival
  • Risk factors for early death
  • Pathological prognostic features
    • Number of normal glomeruli (strong predictor of renal function)
    • Active lesions are associated with renal recovery: active glomerular necrosis and crescents, higher in granulomatosis with polyangiitis
    • Chronic lesions are associated with poor renal prognosis: glomerulosclerosis higher in microscopic polyangiitis or MPO ANCA than in granulomatosis with polyangiitis or PR3 ANCA patients (Clin Rheumatol 2017;36:1949, Nephrol Dial Transplant 2005;20:96)
Case reports
  • Cyclophosphamide and prednisolone to induce remission
  • Maintenance therapy with less toxic drugs such as mycophenolate mofetil, azathioprine
  • Plasmapheresis or plasma exchange in refractory cases
  • Rituximab (anti-CD20) for induction or relapses (Nat Rev Rheumatol 2014;10:484)
Microscopic (histologic) description
  • Pathological classification (J Am Soc Nephrol 2010;21:1628)
    • Focal (> 50% normal glomeruli)
    • Crescentic (> 50% cellular or fibrocellular crescents):
      • Crescents containing > 10% cellularity included
      • Fibrous crescents not counted
    • Mixed (heterogeneous glomerular lesions, none predominating as > 50%)
    • Sclerotic (> 50% global glomerulosclerosis, defined as > 80% of capillary tuft sclerosed)
  • Focal segmental fibrinoid necrosis (glomerular basement membrane is disrupted in areas of necrosis)
  • Extracapillary proliferation with the accumulation of macrophages and epithelial cells in Bowman space (age of crescents: cellular, fibrocellular, fibrous)
  • Karyorrhectic debris and fibrin thrombi are frequently seen within the affected glomerular capillary lumens
  • Active periglomerular inflammation and rupture of Bowman capsule
  • Sometimes periglomerular granulomatous inflammation
  • Normal glomeruli usually present
  • Endocapillary hypercellularity, typical of immune complex mediated glomerulonephritides, is lacking
  • Variable inflammation, predominantly composed of lymphocytes, histiocytes, plasma cells and sometimes brisk number of eosinophils
  • Granulomas suggest the possibility of underlying granulomatous with polyangiitis or eosinophilic granulomatous with polyangiitis
    • Note that an apparent interstitial granuloma adjacent to a disrupted Bowman capsule does not carry the same connotation
  • Vasculitis 5 - 35%; involves small arteries, arterioles, capillaries, venules
  • Interlobular arteries usually site affected in systemic vasculitis
  • Leukocytoclastic vasculitis pattern (neutrophils, fibrinoid necrosis)
  • Necrotizing, leukocytoclastic angiitis of the medullary vasa recta (frequently associated with interstitial hemorrhage and the presence of neutrophilic tubulitis and neutrophils within tubular lumens) (Colvin: Diagnostic Pathology: Kidney Diseases, 2nd Edition, 2015, Zhou: Silva's Diagnostic Renal Pathology, 2nd Edition, 2017)
Microscopic (histologic) images

Contributed by Ana Belén Larqué, M.D, Ph.D.
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Arterial wall with fibrinoid necrosis

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Cellular crescent

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Segmental fibrinoid necrosis of glomerular tufts

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Interstitial inflammation

Immunohistochemistry & special stains
  • Immunohistochemistry not used for diagnosis
  • PAS, Jones silver and trichrome are used to evaluate morphology but are not specific for the type of glomerular disease
Immunofluorescence description
  • Pauci-immune glomerular pattern (weak ≤ 1+) granular staining for IgG, IgM, IgA, C3 and C1q
  • There is no evidence of glomerular immunodeposits
  • Active crescents and fibrinoid necrosis stain for fibrin
  • Reference: Am J Pathol 1989;135:921
Immunofluorescence images

Contributed by Ana Belén Larqué, M.D, Ph.D.
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Segmental staining for fibrinogen

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Arterial wall staining for fibrinogen

Electron microscopy description
  • Electron microscopy generally contributes little, mainly recapitulating the changes seen on light microscopy
  • Subendothelial edema, microthrombosis and degranulation of neutrophils are present but immune deposits are absent (J Am Soc Nephrol 2010;21:1628)
Sample pathology report
  • Left kidney, biopsy:
    • Focal necrotizing and crescentic ANCA glomerulonephritis
      • Adequacy: adequate (cortex 80%, medulla 20%)
      • Microscopic description: 13 glomeruli, 5 of these exhibited crescents (one with fibrinoid necrosis), including 2 cellular crescents and 3 fibrocellular crescents. Fibrosis occupying 30% of the interstitium with minimal lymphoplasmacytic infiltrate. There was no evidence of extraglomerular arteritis.
      • Immunofluorescence microscopy: Number of glomeruli: 3. There were no deposits of IgA, IgM, IgG, C3, C1q or fibrin.
Differential diagnosis
Board review style question #1

    What is the most likely diagnosis on this biopsy?

  1. Focal segmental glomerulosclerosis
  2. Minimal changes disease
  3. Myeloma cast nephropathy
  4. Pauci-immune necrotizing and crescentic glomerulonephritis, ANCA associated
Board review style answer #1
D. Pauci-immune necrotizing and crescentic glomerulonephritis, ANCA associated

Comment Here

Reference: Pauci-immune complex crescentic glomerulonephritis / ANCA associated vasculitis
Board review style question #2
    Which of the following signs and symptoms are common in ANCA related glomerulonephritis?

  1. Edema
  2. Lipiduria
  3. Nephrotic range proteinuria
  4. Rapidly progressive renal failure
Board review style answer #2
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