Key Facts

Goodpasture syndrome (anti-GBM disease) is an autoimmune condition caused by circulating antibodies directed against the non-collagenous (NC1) domain of the α3 chain of type IV collagen in the glomerular and alveolar basement membranes. It typically presents as a pulmonary-renal syndrome.

Epidemiology

Rare — annual incidence approximately 0.5-1 per million. Bimodal age distribution: young men (20-30 years) more commonly present with pulmonary-renal syndrome; older patients (60-70 years) present with renal-limited disease. 60-80% have both renal and pulmonary involvement. Approximately 10-15% of patients also have concurrent ANCA positivity (usually anti-MPO).

Aetiology

The autoimmune response is directed against a normally cryptic epitope in the NC1 domain of the α3(IV) collagen chain. Triggers for epitope exposure include:

• Smoking (strongest environmental risk factor for pulmonary involvement)
• Hydrocarbon/solvent exposure
• Respiratory infections (especially influenza)
• Genetic susceptibility: HLA-DR15 (positive association), HLA-DR1/DR7 (protective)
• Cocaine inhalation
• Lithotripsy (case reports)

Pathophysiology

Anti-GBM antibodies bind to the α3(IV) collagen in the GBM, activating complement and recruiting neutrophils. This causes a rapidly progressive crescentic glomerulonephritis with crescent formation in >50% of glomeruli. In the lungs, antibodies bind to the alveolar basement membrane causing capillaritis and diffuse alveolar haemorrhage. Pulmonary involvement requires a "second hit" (smoking, infection, fluid overload) that increases alveolar capillary permeability and exposes the alveolar basement membrane to circulating antibodies.

Pulmonary-Renal Presentation

• Haemoptysis: ranges from blood-streaked sputum to massive haemoptysis
• Dyspnoea and cough
• Rapidly progressive renal failure: oliguria/anuria, oedema, hypertension
• Malaise, fatigue, weight loss
• Haematuria (often macroscopic)
• Crackles on auscultation (alveolar haemorrhage)

Renal-Limited Disease

• Features of rapidly progressive glomerulonephritis without haemoptysis
• More common in older patients

Red Flags

• Haemoptysis with rising creatinine — assume pulmonary-renal syndrome until proven otherwise
• Oliguria/anuria (late presentation, poor renal prognosis)
• Massive haemoptysis (life-threatening)
• Rapidly falling haemoglobin without external bleeding (occult alveolar haemorrhage)
• New-onset hypertension with haematuria

Bedside

• Urinalysis: haematuria (often with red cell casts), proteinuria
• SpO₂: may be low (alveolar haemorrhage)
• BP: may be elevated

Bloods

• Anti-GBM antibodies: diagnostic — request urgently; ELISA or Biosensor assay
• ANCA: check concurrently — 10-15% are dual anti-GBM/ANCA positive
• U&Es: rapidly rising creatinine, hyperkalaemia
• FBC: anaemia (haemorrhage), may have leucocytosis
• CRP/ESR: raised
• Complement (C3/C4): normal (unlike SLE)
• Coagulation screen: exclude coagulopathy
• ABG: hypoxaemia

Imaging

• CXR: bilateral alveolar infiltrates (alveolar haemorrhage) — may be normal if renal-limited
• HRCT: ground-glass opacities (acute haemorrhage); may show crazy paving
• Renal ultrasound: normal-sized kidneys (acute disease); small kidneys suggest chronic damage

Special Tests

• Renal biopsy: crescentic glomerulonephritis with linear IgG staining on immunofluorescence — pathognomonic
• BAL: progressively bloodier aliquots (DAH), haemosiderin-laden macrophages
• DLCO: paradoxically raised (Hb in alveolar space absorbs CO) — supports occult DAH
• Lung biopsy: rarely needed; shows capillaritis with linear IgG on immunofluorescence

Non-pharmacological

• Medical emergency: admit immediately, involve renal and respiratory teams
• Stop smoking urgently: reduces pulmonary haemorrhage risk
• Avoid fluid overload: exacerbates pulmonary haemorrhage

Pharmacological

• Plasma exchange (plasmapheresis): daily exchanges (60 ml/kg or 4L) for 14 days or until anti-GBM undetectable — removes circulating antibodies
• Cyclophosphamide: 2-3 mg/kg/day PO (adjust for age and renal function) for 2-3 months; OR IV pulse 15 mg/kg (max 1.2 g) every 2 weeks
• Methylprednisolone: 500 mg-1 g IV daily for 3 days, then prednisolone 1 mg/kg/day (max 60 mg) tapering over 6 months
• Maintenance: typically NOT required as anti-GBM disease rarely relapses (<5%) once antibodies clear — unlike ANCA vasculitis
• Dialysis: if required for acute renal failure; may be temporary or permanent

Surgical/Interventional

• Renal transplantation: consider once anti-GBM antibodies undetectable for ≥6 months and disease quiescent; recurrence in transplant rare (~5%)

Referral Criteria

• Emergency nephrology referral — same day
• Respiratory if significant pulmonary haemorrhage
• Renal transplant assessment if ESRD
• ICU if massive haemoptysis or severe renal failure with complications

Prognosis critically depends on renal function at presentation. Patients presenting with creatinine <500 μmol/L and not requiring dialysis have >80% 1-year renal survival with prompt treatment. Those requiring dialysis at presentation have <10% chance of renal recovery. Overall 1-year survival is >90% with treatment. Anti-GBM disease rarely relapses (<5%) — unlike ANCA vasculitis. Dual anti-GBM/ANCA-positive patients have intermediate prognosis and higher relapse risk. Untreated anti-GBM disease has near 100% mortality.

Prognostic Factors at Presentation

Pulmonary-Renal Syndromes — Differential