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Kidney non-tumor

Primary glomerular diseases

Rapidly progressive (crescentic) glomerulonephritis


Reviewers: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 13 February 2014, last major update July 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● Rapid, usually irreversible, loss of renal function (usually 50% decline in glomerular filtration rate within 3 months), with glomerular crescent formation in 50-75% of biopsied glomeruli (eMedicine, Wikipedia)
● Also called extracapillary proliferative glomerulonephritis, because cell proliferation is primarily in Bowman’s space

Etiology
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● Due to deposition of fibrin, epithelial cells and inflammatory cells; may have various causes

Clinical features
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● Symptoms of nephritic syndrome, nephrotic syndrome and renal failure
● Unresponsive to steroids
● Causes death within weeks if untreated
● Prominent feature is crescents, the end result of damage to glomerular basement membrane or Bowman's capsule
● Crescents affect 50% of glomerular circumference, 70% of glomeruli

Case reports
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● 14 year old boy with Henoch-Schönlein Vasculitis and familial Mediterranean fever (Pediatr Rheumatol Online J 2009;7:8)
● 67 year old man with AL amyloidosis (Nephrol Dial Transplant 2010;25:2786)
● After Hepatitis B infection (Mod Pathol 1992;5:262)
● Associated with IgA myeloma (Nephron Extra 2011;1:69)

Gross description
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● Enlarged, pale kidneys with cortical petechial hemorrhages

Micro description
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● Crescents in glomeruli are proliferation of parietal epithelium of Bowman’s capsule with macrophages, neutrophils, lymphocytes, fibrin and collagen
● Also see glomerular capillary collapse, atrophic tubules and interstitial inflammation

Micro images
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Various images (H&E and PAS)

           
PAS-Silver stain and immunofluorescence


Cellular crescents (PAS)


Cellular crescent


Crescent with necrotizing area on Trichrome


Fibrinogen in crescent IF


Linear IgG in Goodpasture's syndrome

Virtual slides
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Numerous crescents

Electron microscopy description
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● Wrinkling and focal disruptions in glomerular basement membrane

Differential diagnosis
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Fibrillary glomerulonephritis: 20-30 nm fibrils in glomeruli by EM


3 subtypes based on immunofluorescence and EM

TYPE 1: Anti-glomerular basement membrane antibody crescentic glomerulonephritis (15%)

General
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Goodpasture’s syndrome: antibody to alpha 3 chain of type 4 collagen (part of non-collagenous domain) in lung alveolar basement membrane; associated with smoking and HLA-DRB1
● Usually young adult males with pulmonary involvement or age 50+ women limited to kidney
● Pulmonary hemorrhage present, treated with plasmapheresis, steroids and cytotoxic agents
● Most cases of Goodpasture’s are associated with rapidly progressive glomerulonephritis; but only 50% have both renal and pulmonary syndromes
Laboratory: 1/3 have circulating anti-neutrophil cytoplasmic antibodies (ANCA), especially ANCA specific for myeloperoxidase

Case reports
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● Co-existing vasculitis (Arch Pathol Lab Med 1980;104:300)

Micro description
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● Hypercellular glomeruli, crescents in > 50% glomeruli at time of biopsy, variable neutrophils, no / rare intracapillary cell proliferation and earliest lesion is focal segmental fibrinoid necrosis

Micro images
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Various images


Diffuse linear staining for IgG

Immunofluorescence
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● Diffuse linear staining of glomerular basement membrane, IgG > IgM, also C3 and focal fibrin in capillary loops, IgG should be at least 3+ or 4+ and no staining in mesangium

Electron microscopy description
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● No deposits; fibrin at glomerular basement membrane breaks

Differential diagnosis
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Based on clinical presentation:
● Microscopic polyarteritis
● Wegener’s granulomatosis
● Similar immunofluorescent findings in diabetic nephropathy
● SLE


TYPE 2: Immune complex crescentic glomerulonephritis (35%)

General
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● Immune complex deposition with complement activation due to postinfectious glomerulonephritis, types I and II membranoproliferative glomerulonephritis, cryoglobulinemic glomerulonephritis, SLE, IgA nephropathy, Henoch-Schonlein purpura and idiopathic
● Usually children
● Must treat underlying disease; plasmapheresis NOT helpful (in contast to anti-GBM glomerulonephritis)

Micro description
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● Depends on underlying glomerular disease
● Mild-moderate necrosis of glomerular segments adjacent to crescents, less than types 1 or 3
● Various combinations of capillary wall thickening and endocapillary cell proliferation

Immunofluorescence
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● Lumpy bumpy for IgG and C3 (like postinfectious)

Electron microscopy description
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● Immune complex deposits as subepithelial humps or mesangial deposits, fibrin at glomerular basement membrane breaks


TYPE 3: Pauci-immune crescentic glomerulonephritis (50%)

General
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● No anti-glomerular basement membrane antibodies, no immune complexes (hence called ‘pauci-immune’)
● Usually elderly
● Either limited to kidney or associated with clinical vasculitis (Wegener’s granulomatosis, microscopic polyarteritis)
● Rare complication of Sjogren's syndrome (J Formos Med Assoc 2011;110:473)
● Often have serum C-ANCA (against proteinase 3 PR3-ANCA; associated with Wegener’s) or P-ANCA (against myeloperoxidase MPO-ANCA; in those without extrarenal vasculitis)
● Those with microscopic polyarteritis have either
● Better prognosis than type 1
● Poorer prognosis if high serum creatinine at presentation and focal C3c depositions in areas of glomerular and arteriolar fibrinoid necrosis (Int J Immunopathol Pharmacol 2012;25:287)

Micro description
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● Resembles type 1

Micro images
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Various images

Immunofluorescence
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● Ig negative, possibly C3 and fibrin / fibrinogen with crescents (pauci-immune only refers to intensity of staining and does not imply that an immune process does not mediate the injury)

Electron microscopy description
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● Same as type 1 (no deposits, focal segmental glomerular necrosis and fibrin at glomerular basement membrane breaks)

End of Kidney non-tumor > Primary glomerular diseases > Rapidly progressive (crescentic) glomerulonephritis

Ref Updated: 6/5/12


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