Goodpasture Syndrome - Anti-GBM Disease

Goodpasture syndrome is an autoimmune condition characterized by rapidly progressive glomerulonephritis, pulmonary hemorrhage, and deposits of antibodies to the glomerular base membrane (GBM). In anti-GBM disease, 45% of cases show kidney and pulmonary involvement (Goodpasture syndrome), 5% of cases have isolated lung involvement, and 50% of cases involve only the kidney.

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 is consistent with genetic predisposition to autoimmunity
HLA-DR15 and HLA-DR4 (positive); HLA-DR7 and HLA-DR1 (negative)

Pathophysiology

Antibodies formed are directed against the non-collagenous-1 (NC-1) domain of type IV collagen (mainly alpha-3 chain)
Linear deposits of antibodies are present in the basement membrane of renal and pulmonary organs
Antibodies damage the glomerular and alveolar basement membrane

Clinical Presentation

Identification of disease often delayed because Goodpasture syndrome 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, the 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 is the main cause of anemia
Outcomes
- Untreated – universally poor outcome
- With treatment, no dialysis, and Cr<6 mg/dL at one year – patient (83%) and patient's kidney (82%) survival rates
- With dialysis at one year – patient and patient's renal survival rates drop to 65% and 8% at one year, respectively

Treatment

Early diagnosis and treatment correlates with better outcome
Cytotoxic drugs and plasma exchange are the cornerstone treatment of anti-GBM disease
- Plasmapheresis is believed to remove anti-GBM antibodies responsible for initiating damage as well as secondary circulating mediators
Remission may follow intensive plasmapheresis treatment combined with corticosteroids and cytotoxic agents

Indications for Testing

Patient presenting with pulmonary hemorrhage and renal disease

Laboratory Testing

Serum GBM antibody assays
- Faster and more reliable than the less sensitive indirect immunofluorescent test on normal kidney sections
- 2-3% of patients may have antibodies that are undetectable by current methods
ANCA antibody testing
- Approximately 30% of anti-GBM positive samples are also ANCA positive
- Rule out other causes of rapidly progressive glomerulonephritis
Nonspecific testing
- CBC – frequently reveals anemia
- Creatinine and blood urea nitrogen – may be elevated
- Erythrocyte sedimentation rate – usually elevated
- Urinalysis – may detect hematuria

Histology

Renal biopsy
- Diagnostic confirmation and assessment of renal prognosis
- Severe crescentic glomerulonephritis – linear IgG deposits in the GBM

Differential Diagnosis

Pulmonary hemorrhage
- ANCA-associated systemic vasculitis (eg, Churg-Strauss syndrome)
- Infections
  - Bacterial
    - Mycobacterium tuberculosis
  - Viral
    - Dengue fever
    - Leptospirosis
    - Yellow fever
    - Ebola virus
  - Fungal
    - Pneumocystis jiroveci
    - Aspergillus
- Löffler syndrome
- Lung cancer
- Cryptogenic organizing pneumonia
Renal disease
- Immune complex glomerulonephritis (poststreptococcal glomerulonephritis, lupus nephritis, IgA nephropathy with crescents)
- ANCA-associated pauci-immune crescentic glomerulonephritis
- Polyarteritis nodosa
Combined renal and pulmonary disease
- ANCA-associated systemic vasculitis (Wegner granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome)

Monitor treatment
- Anti-GBM titers – should decline with effective treatment
- Serum creatine levels – assess renal function
- Hemoglobin levels – monitor lung hemorrhage
Monitor side effects of drugs
- Surveillance for infections due to immunosuppressive drugs
- White blood cell count for drug cytotoxicity
- Platelet count to assess the effect of plasmapheresis

Tests generally appear in the order most useful for common clinical situations

Test name: Glomerular Basement Membrane Antibody Panel

ARUP #: 0051001

Methodology: Semi-Quantitative Multi-Analyte Fluorescent Detection/Qualitative

Use:

Detect and quantify GBM antibodies for diagnosis of Goodpasture syndrome

Panel includes GBM antibodies IgA and IgG

Limitations:

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

2-3% may have antibodies undetectable by current methods

Test name: MPO/PR-3 (ANCA) Antibodies

ARUP #: 0050707

Methodology: Semi-Quantitative Multi-Analyte Fluorescent Detection

Use:

Rule out other causes of glomerulonephritis

Components include the myeloperoxidase and serine protease 3 antibodies

Test name: Renal Pathology Special Studies

ARUP #: arup029

Methodology: Microscopic Exam

Use:

Confirm positive glomerular basement membrane antibody test results

Detect presence of anti-GBM antibodies in renal biopsy

Note: Request staining for anti-GBM antibodies and C3

Test name: CBC with Platelet Count

ARUP #: 0040002

Methodology: Automated Cell Count

Use:

Non-specific testing

Monitor anemia

Test name: Urea Nitrogen, Serum or Plasma

ARUP #: 0020023

Methodology: Quantitative Spectrophotometry

Use:

Non-specific testing

Monitor renal failure

Test name: Creatinine Clearance, Urine

ARUP #: 0020474

Methodology: Quantitative Spectrophotometry/Enzymatic/Calculation

Use:

Non-specific testing

Monitor renal failure

Test name: Sedimentation Rate, Westergren (ESR)

ARUP #: 0040325

Methodology: Westergren

Use:

Non-specific testing

Assess degree of inflammation

Test name: Urinalysis, Complete

ARUP #: 0020350

Methodology: Reflective Photometry/Microscopic by Yellow IRIS

Use:

Non-specific testing

Detect hematuria, proteinuria

Additional Tests Available

Test name: Glomerular Basement Membrane Antibody, IgG by Multi-Analyte Fluorescent Detection

ARUP #: 0051000

Methodology: Semi-Quantitative Multi-Analyte Fluorescent Detection

Comments:

Test name: Glomerular Basement Membrane Antibodies, IgA & IgG (IFA)

ARUP #: 0049190

Methodology: Indirect Fluorescent Antibody

Comments:

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

Test name: Glomerular Basement Membrane Antibody, IgG (IFA)

ARUP #: 0049191

Methodology: Indirect Fluorescent Antibody

Comments:

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

Test name: Glomerular Basement Membrane Antibody, IgA (IFA)

ARUP #: 0049192

Methodology: Indirect Fluorescent Antibody

Comments:

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

General

ARUP Institute for Clinical and Experimental Pathology®

Comprehensive Review: July 2011
Last Update: July 2011

Microscopic Polyangiitis

Polyarteritis Nodosa

Scleroderma

Vasculitis