Antiglomerular Basement Membrane Disease - Goodpasture Syndrome

  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Pulmonary hemorrhage or symptoms of alveolitis
    • Hemoptysis
    • Dry cough
    • Shortness of breath
    • Consolidation on chest x-ray
  • Renal disease (particularly rapid, progressive renal disease) alone or in combination with pulmonary disease
    • Hematuria
    • Proteinuria

Laboratory Testing

  • Diagnostic testing – serum glomerular basement membrane (GBM) antibody IgG
    • IgG antibody to GBM antigen detected by either indirect fluorescent antibody (IFA) or multiplex bead assay supports diagnosis
      • Combined result of both assays (IFA and multiplex bead) performed during initial evaluation improves diagnostic sensitivity for disease
    • Positive result in one or both assays should be confirmed by renal biopsy unless contraindicated
    • Multiplex bead assay is faster and more reliable than the less specific IFA test on normal kidney sections
    • Small percentage of patients may have antibodies that are undetectable by current methods
  • Nonspecific testing – assist in excluding other diagnoses and identifying organ dysfunction
    • CBC 
    • Creatinine and blood urea nitrogen (BUN)
      • Elevated if significant kidney damage has occurred
    • C-reactive protein (CRP)
      • Usually elevated
      • Preferred test to detect inflammation processes (Choosing Wisely, 2016)
      • If CRP not available, order erythrocyte sedimentation rate (ESR)
    • Urinalysis
      • May show red blood cells (RBCs), blood, and protein
    • Antineutrophil cytoplasmic antibody (ANCA) testing
      • Moderate number of anti-GBM patients are also ANCA positive
      • May support diagnosis of other glomerulonephritis (type 2)
      • Important to rule out other causes of rapidly progressive glomerulonephritis (eg, other vasculitis)

Histology

  • Renal biopsy
    • Use for diagnosis and assessment of prognosis

Differential Diagnosis

  • Monitor treatment
    • Antiglomerular basement membrane (GBM) antibody testing
      • Concentrations should decline with effective treatment but may not be reliable
      • Increased antibody concentrations following remission may be indicative of relapse
  • Monitor side effects of drugs
    • White blood cell (WBC) count – for drug cytotoxicity
    • Platelet count – assess effect of plasmapheresis
    • Serum creatinine levels –  assess renal function
    • Hemoglobin levels –  monitor lung hemorrhage
    • Surveillance for infections due to immunosuppressive drugs

Antiglomerular basement membrane (anti-GBM) disease (Goodpasture syndrome) is an autoimmune condition characterized by progressive damage to collagen, resulting in damage to the lung parenchyma and the kidney basement membrane. Lung damage results in hemorrhage with cough and shortness of breath. Deposits in the kidneys result in glomerulonephritis and renal disease. The symptoms can progress over time or be rapidly progressive. Anti-GBM is categorized as a small-vessel vasculitis (Chapel Hill, 2012).

Classification

  • Classification of glomerulonephritis (GN) (Sethi, 2016) based on kidney biopsy
    • Immune complex GN
    • Pauci-immune GN
    • Anti-GBM
    • Monoclonal  Ig GN
    • C3 glomerulopathy
  • Classification of crescentic glomerulonephritis (Parmar, 2017)
    • Type I – anti-GBM
    • Type II – immune-complex medications
    • Type III – few or no immune complexes (antineutrophil cytoplasmic antibody [ANCA] associated)
    • Type IV – combination

Epidemiology

  • Incidence – <1/million worldwide (Hellmark, 2014)
    • Accounts for 10-20% of patients presenting with acute renal failure due to rapidly progressive glomerulonephritis
      • 0.4% of children in end-stage renal disease
      • ~50% of adults have renal damage when assessed at 6 months (Sethi, 2016)
      • 20% of patients present with pulmonary renal syndrome
    • Very rare in pediatric population
  • Age – 2 peaks
    • 20-30 years and 50-70 years
  • Ethnicity – Caucasians predominate
  • Sex – M:F, equal

Inheritance

  • High prevalence of DRB1*1501 and *1502 haplotypes – consistent with genetic predisposition to autoimmunity
  • Typical HLA types
    • HLA-DR15 and HLA-DR4 – positive
    • HLA-DR7 and HLA-DR1 – negative

Pathophysiology

  • Antibodies formed are directed against noncollagenous-1 domain of type IV collagen (mainly alpha-3 chain)
  • Linear deposits of antibodies develop in basement membrane of renal and pulmonary organs
  • Antibodies damage glomerular and alveolar basement membrane
  • Vasculitic process involves glomerular and pulmonary capillaries

Clinical Presentation

  • Adults
    • Identification of disease is often delayed because anti-GBM disease is rare and is an unusual cause of hemoptysis and/or renal failure (pulmonary-renal syndrome)
    • Pulmonary
      • Mild to severe disease presentation
      • Pulmonary hemorrhage and hemoptysis – hemoptysis more common in smokers
      • Pulmonary involvement sometimes precedes nephritis – main cause of morbidity and mortality
      • Pulmonary opacities on chest radiography
      • Disease course may be dominated by recurrent hemoptysis or life-threatening pulmonary hemorrhage
    • Renal
      • Early presenting signs and symptoms – oliguria, proteinuria, hematuria
      • Renal involvement frequently progresses over a matter of days to acute renal failure
        • Acute glomerulonephritis – usually rapidly progressive type/crescentic glomerulonephritis
      • Anemia – pulmonary hemorrhage main cause of anemia
  • Pediatrics
    • Presentation more likely to be combined pulmonary/renal diseases
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay and IFA 2008403
Method: Semi-Quantitative Multiplex Bead Assay/Qualitative Indirect Fluorescent Antibody

Follow-up 

A positive result in one or both assays should be confirmed by renal biopsy

Renal Pathology Special Studies

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Urea Nitrogen, Serum or Plasma 0020023
Method: Quantitative Spectrophotometry

Creatinine, Serum or Plasma 0020025
Method: Quantitative Enzymatic

Limitations 

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite), but only when concentrations are at or above those expected during acetaminophen overdose

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

ANCA-Associated Vasculitis Profile (ANCA/MPO/PR-3) with Reflex to ANCA Titer 2006480
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Guidelines

Chapter 14: Anti-glomerular basement membrane antibody glomerulonephritis. Kidney Int Suppl (2011). 2012; 2(2): 240-242. PubMed

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Jun 2017]

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed

General References

Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture's disease (anti-GBM). J Autoimmun. 2014; 48-49: 108-12. PubMed

Ooi JD, Holdsworth SR, Kitching R. Advances in the pathogenesis of Goodpasture's disease: from epitopes to autoantibodies to effector T cells. J Autoimmun. 2008; 31(3): 295-300. PubMed

Parmar M, Bhimji S. Glomerulonephritis, Crescentic. StatPearls. Treasure Island (FL) [Accessed: Jun 2017]

Pedchenko V, Bondar O, Fogo AB, Vanacore R, Voziyan P, Kitching R, Wieslander J, Kashtan C, Borza D, Neilson EG, Wilson CB, Hudson BG. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med. 2010; 363(4): 343-54. PubMed

Sethi S, Haas M, Markowitz GS, D'Agati VD, Rennke HG, Jennette C, Bajema IM, Alpers CE, Chang A, Cornell LD, Cosio FG, Fogo AB, Glassock RJ, Hariharan S, Kambham N, Lager DJ, Leung N, Mengel M, Nath KA, Roberts IS, Rovin BH, Seshan SV, Smith RJ, Walker PD, Winearls CG, Appel GB, Alexander MP, Cattran DC, Casado CA, Cook T, De Vriese AS, Radhakrishnan J, Racusen LC, Ronco P, Fervenza FC. Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN. J Am Soc Nephrol. 2016; 27(5): 1278-87. PubMed

Williamson SR, Phillips CL, Andreoli SP, Nailescu C. A 25-year experience with pediatric anti-glomerular basement membrane disease. Pediatr Nephrol. 2011; 26(1): 85-91. PubMed

Zhou X, Lv J, Zhao M, Zhang H. Advances in the genetics of anti-glomerular basement membrane disease. Am J Nephrol. 2010; 32(5): 482-90. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Jaskowski TD, Martins TB, Litwin CM, Hill HR. Comparison of four enzyme immunoassays for the detection of immunoglobulin G antibody against glomerular basement membrane. J Clin Lab Anal. 2002; 16(3): 143-5. PubMed

Litwin CM, Mouritsen CL, Wilfahrt PA, Schroder MC, Hill HR. Anti-glomerular basement membrane disease: role of enzyme-linked immunosorbent assays in diagnosis. Biochem Mol Med. 1996; 59(1): 52-6. PubMed

Medical Reviewers

Last Update: September 2017