Antiglomerular Basement Membrane Disease - Goodpasture Syndrome

Diagnosis

Indications for Testing

  • Pulmonary hemorrhage and/or renal disease

Laboratory Testing

  • Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
    • CBC – frequently reveals anemia
    • Creatinine and blood urea nitrogen – may be elevated
    • Erythrocyte sedimentation rate (ESR)/C-reactive protein(CRP) – usually elevated
    • Urinalysis – hematuria common if renal involvement present
    • ANCA antibody testing
      • Approximately 30% of anti-GBM positive samples are also ANCA positive
      • Important to rule out other causes of rapidly progressive glomerulonephritis
  • Serum glomerular basement membrane (GBM) antibody assays
    • Faster and more reliable than the less specific indirect immunofluorescent test on normal kidney sections
    • 2-3% of patients may have antibodies that are undetectable by current methods

Histology

  • Renal biopsy
    • Useful for diagnostic confirmation and assessment of renal prognosis
    • Typical histology - severe crescentic glomerulonephritis – linear IgG deposits in the GBM

Differential Diagnosis

Monitoring

  • Monitor treatment
    • Anti-GBM antibody testing – titers should decline with effective treatment, but may not be reliable
      • Increased antibody levels following remission may be indicative of relapse
  • Monitor side effects of drugs
    • WBC count – for drug cytotoxicity
    • Platelet count – to assess the effect of plasmapheresis
    • Serum creatinine levels –  to assess renal function
    • Hemoglobin levels –  to monitor lung hemorrhage
    • Surveillance for infections due to immunosuppressive drugs

Clinical Background

Antiglomerular basement membrane disease (Goodpasture syndrome) is an autoimmune condition characterized by rapidly progressive glomerulonephritis, pulmonary hemorrhage, and deposits of antibodies to the glomerular basement membrane (GBM).  It is categorized as a vasculitis (Chapel Hill 2012).

Epidemiology

  • Incidence – 1-2/1,000,000
    • 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
      • 20% of patients present with pulmonary renal syndrome
    • Very rare in pediatric population
  • Age –  2 peaks
    • 20-30 years – male predominance
    • 50-70 years – female predominance
  • Ethnicity – Caucasians predominate

Inheritance

  • High prevalence of the 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 the noncollagenous-1 (NC-1) domain of type IV collagen – mainly alpha-3 (IV) chain
  • Linear deposits of antibodies develop in the basement membrane of renal and pulmonary organs
  • Antibodies damage the glomerular and alveolar basement membrane
  • Vasculitic process involves glomerular and pulmonary capillaries

Clinical Presentation

  • Identification of disease often delayed because anti-GBM disease is not the most common cause of hemoptysis or renal failure (pulmonary-renal syndrome)
  • Pulmonary
    • Pulmonary hemorrhage and hemoptysis – hemoptysis more common in smokers
    • Pulmonary involvement often 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
      • Immediate treatment required to avoid irreversible kidney damage
    • Acute glomerulonephritis – usually rapidly progressive type/crescentic glomerulonephritis
  • Anemia – pulmonary hemorrhage main cause of anemia
  • Outcomes
    • Untreated – universally poor outcome
    • With treatment, no dialysis, and creatinine <6 mg/dL at one year – good patient and patient's kidney survival rates

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay and IFA 2008403
Method: Semi-Quantitative Multiplex Bead Assay/Qualitative Indirect Fluorescent Antibody

To detect and monitor glomerular basement membrane (GBM) antibodies  in suspected or established anti-GBM disease

Panel includes GBM antibodies IgG

False-positive results may occur due to reactivity against other chains of type IV collagen  
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

Rule out ANCA-associated glomerulonephritis

Components include myeloperoxidase and serine protease 3 antibodies

   
Renal Pathology Special Studies

Confirm positive GBM antibody results

Detect presence of anti-GBM antibodies in renal biopsy

Note: Request staining for anti-GBM antibodies and C3

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

Evaluate for anemia in anti-GBM disease

Monitor side effects of immunosuppressive agents in anti-GBM disease

May help in ruling out infectious process

   
Urea Nitrogen, Serum or Plasma 0020023
Method: Quantitative Spectrophotometry

Aid in diagnosis of renal involvement in anti-GBM disease

Monitor renal failure

   
Creatinine, Serum or Plasma 0020025
Method: Quantitative Enzymatic

Aid in diagnosis of renal involvement in anti-GBM disease

Monitor renal failure

   
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Screen for hematuria, proteinuria, and RBC casts

   
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Initial evaluation for suspected vasculitis

   
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Initial evaluation for suspected ANCA-associated vasculitis

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay 0051000
Method: Semi-Quantitative Multiplex Bead Assay
Glomerular Basement Membrane Antibody, IgG (IFA) 0049191
Method: Indirect Fluorescent Antibody

Less specific than the quantitative tests for circulating antibodies; all positive results need to be confirmed by semiquantitative tests and/or renal biopsy