Anti-Glomerular Basement Membrane Antibody Disease

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Anti-Glomerular Basement Membrane Antibody Disease

• Morning Report
• 10/3/08
• Dave Rometo

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Outline

• RPGN
• Anti-GBM disease
• Pathogenesis
• Epidemiology
• Clinical presentation
• Diagnosis
• Treatment
• Prognosis

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RPGN

• Rapidly progressive (crescenteric)
  glomerulonephritis
• Increase in Cr over days to weeks
• gt50 loss of kidney function
• Extensive (gt50) crescent formation
• Proliferative or necrotizing injury to glomerular
  capillary wall (rents) letting plasma and
  fibrinogen into Bowmans space, forming fibrin,
  bringing in macrophages, T cells, releasing
  cytokines.

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RPGN

• Type 1 Anti-GMB
• Type 2 Immune Complex
• IgA, postinfectious, lupus, mixed
  cryoglobulinemia
• Type 3 Pauci-immune
• Most are P-ANCA, some ANCA neg
• Type 4 Double-antibody positive
• Features of type 1 and 3

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RPGN Histopathology
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RPGN Clinical Summary

• Acute macroscopic hematuria, decreased urine
  output, edema
• Insidious fatigue and edema
• Renal insufficiency, dysmorphic hematuria, red
  cell casts, other casts, proteinuria
• Pulmonary hemorrhage and hemoptysis
• Tests ANCA, anti-GBM antibodies, complement,
  ANA, and renal biopsy
• Treatment pulse steroids, Cytoxan, PLEX

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Anti-GBM Antibody Disease

• Circulating antibodies against antigen in the GBM
  causing RPGN /- pulmonary hemorrhage
• Goodpastures syndrome if pulm. hemorrhage
• IgG against the NC1 domain of the alpha-3 chain
  of type IV collagen alpha-3(IV) on 2q35-37. The
  epitope is about 9 amino acids long.
• Can rarely be IgA or IgM.
• Alpha-3(IV) is concentrated in glomeruli and
  alveoli
• Prior lung disease is RF for pulm involvement

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Epidemiology

• lt 1 case per million population
• I hear a zebra
• lt 20 of RPGN
• More pulm involvement if lt 30 yo, MgtF
• Isolated RPGN if gt 50 yo, FgtM

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Clinical Presentation

• Like other RPGN ARF, nephritic sediment (look at
  the urine!), non-nephrotic proteinuria
• Alveolar hemorrhage
• 60-70 of pts
• SOB, cough, hemoptysis, infiltrates, high DLCO
• Iron deficiency anemia if prolonged
• Smokers, lung infections, cocaine, hydrocarbon
• Systemic symptoms suggest ANCA vasculitis
• Malaise, weight-loss, fevers, arthralgias

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Diagnosis

• Renal Biopsy
• Necrotizing and crescenteric GN on light
  microscopy
• Immunoflourescence- linear IgG deposition along
  glomerular capillaries
• Serum anti-GBM antibodies
• ELISA confirmed by Western blot
• Kits using recombinant human alpha-3(IV) antigen
  have 100 sens, 100 spec.
• Mayo Clinic send-out. ELISA IgG
• ANCA can have both (Type 4) Wegeners or MPA
• 10-38 of anti-GBMs are ANCA, usually MPO
• Repeat if negative but disease recurs

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Treatment

• Steroids
• Methylprednisolone 15-30 mg/kg up to 1 g over 20
  minutes IV qd x 3 days
• Then oral prednisone 1 mg/kg qd up to 60-80, 9 mo
• Cyclophosphamide (Cytoxan)
• 2 mg/kg/day PO x 3 months
• IV if cant take PO, unreliable, severe renal
  failure and oliguria
• Plasmapheresis
• Qd or qod, 4 liter exchange, 2-3 weeks, albumin

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Prognosis

• Survival correlates with renal impairment at
  presentation
• Creatinine gt 5 gt 75 crescents
• If untreated, death or HD in gt90 of pts
• If need immediate HD or has 100 crescents,
  unlikely to recover renal function
• After treatment, relapse is rare. Higher in
  smokers, hydrocarbon exposure, and ANCA
• Those w/ Cr lt 3, lt 30 crescents do well

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References

• www.utdol.com
• MKSAP14 Nephrology
• The UNC Internal Medicine Residency Experience!