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Anti-Glomerular Basement Membrane Disease (Goodpasture’s Syndrome)

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Overview

Anti-glomerular basement membrane disease (anti-GBM disease, Goodpasture’s syndrome) is a type of rapidly progressive glomerulonephritis (RPG) characterised by the presence of autoantibodies against the alpha-3 chain of type IV collagen which is mostly found in the basement membranes of the glomerulus and alveoli.

Epidemiology

  • Anti-GBM disease is rare with around 1-2 cases per million
  • Its incidence is highest at ages 20-30 and 60-70 years
  • It is more common in men

Risk Factors

  • HLA-DRB1*1501 or HLA-DR4
  • Smoking

Presentation

Due to the presence of anti-GBM antibodies against type IV collagen found in the lungs and glomeruli, patients may present with:

Differential Diagnoses

Granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis)

  • Can also present with haemoptysis, RPG, and nephritic syndrome
  • Patients generally have a history of sinusitis or chronic cough in GPA
  • There may be a ‘saddle-shape’ nose deformity in GPA
  • GPA is associated with c-anti-neutrophil cytoplasmic antibodies (c-ANCA)
  • A renal biopsy shows no deposits of immune complexes

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome)

  • Although EGPA can present with RPG and nephritic syndrome, haemoptysis is less common
  • Patients generally have a history of asthma that tends to be refractory
  • Blood tests show eosinophilia
  • EGPA is associated with perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA)
  • A renal biopsy shows no deposits of immune complexes

Post-streptococcal glomerulonephritis

  • Only features of RPG and haematuria are present, no pulmonary symptoms such as haemoptysis are seen
  • Anti-streptolysin O is elevated
  • Renal biopsy shows immune complex deposition in a granular pattern

Systemic lupus erythematosus (lupus nephritis)

  • Other features of lupus present e.g. malar rash/photosensitivity/hair loss/oral ulcers
  • Anti-nuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies may be elevated
  • Renal biopsy shows immune complex deposition in a granular pattern

Investigations

  • Urea and electrolytes (U&Es):
    • Abnormal
  • Anti-GBM titres:
    • Positive, but may sometimes be negative
  • Renal biopsy:
    • May show crescenteric glomerulonephritis, suggesting RPG
    • May show IgG deposits along the basement membrane

Management

Overview

Management may involve:

  • Removal of circulating anti-GBM antibodies: plasmapheresis
  • Stop further production of anti-GBM antibodies: immunosuppressants (e.g. corticosteroids with cyclophosphamide)
  • Managing end-stage kidney disease if appropriate with haemodialysis or renal transplantation

Complications

Pulmonary haemorrhage

  • Potentially fatal and more common in patients who smoke
  • Patients should be offered help with smoking cessation if appropriate

Chronic kidney disease (CKD)

  • Damage due to inflammation can leave residual renal damage and hence, CKD

Prognosis

  • With early and aggressive treatment, 1-year survival rates are around 80-90%
  • Some may experience relapses, particularly those that continue smoking 

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