Key Facts

Anti-GBM disease is a medical emergency. The speed of diagnosis and initiation of treatment directly determines renal outcome. Every hour of delay before treatment reduces the chance of renal recovery.

Epidemiology

• Rare: 0.5-1 per million/year
• Bimodal age distribution: young males (20-30) and older females (60-70)
• Young patients more likely to have pulmonary involvement
• ~30% of anti-GBM patients are also ANCA positive (double positive – better prognosis)

Aetiology

• Autoimmune: loss of tolerance to alpha-3(IV) collagen (specifically the NC1 domain)
• Triggers: smoking (major risk factor for pulmonary involvement), hydrocarbons, infections, lithotripsy
• HLA-DR15 (DRB1*1501) associated with susceptibility
• HLA-DR1 and DR7 may be protective

Pathophysiology

• Anti-GBM IgG antibodies bind to the NC1 domain of alpha-3(IV) collagen
• Linear antibody deposition along GBM → complement activation → crescentic GN
• Same collagen is present in alveolar basement membrane → pulmonary haemorrhage if membrane disrupted
• Smoking, infection, or fluid overload disrupts alveolar integrity, exposing the antigen
• Rapid progression to irreversible renal failure within days-weeks if untreated

Renal Manifestations

• RPGN: rapidly declining renal function, oliguria/anuria
• Haematuria: macroscopic or microscopic with red cell casts
• Proteinuria: usually subnephrotic
• Hypertension: variable

Pulmonary Manifestations (Goodpasture Syndrome)

• Haemoptysis: ranging from mild to massive life-threatening
• Dyspnoea, cough
• Bilateral alveolar infiltrates on CXR
• Hypoxia
• More common in smokers and young males

Constitutional

• Malaise, fatigue, weight loss
• Fever (less common than in ANCA vasculitis)

Red Flags

• Massive haemoptysis → ICU, emergency plasma exchange
• Rapidly rising creatinine → start treatment immediately (do not wait for biopsy results)
• Anuric at presentation → renal recovery unlikely but still treat to preserve residual function

Urgent Investigations

• Anti-GBM antibodies (serum ELISA): positive in >95%; result within hours in many labs
• ANCA: 30% of anti-GBM patients are also ANCA positive
• U&Es: rapidly rising creatinine
• Urinalysis: haematuria, red cell casts, proteinuria
• FBC: anaemia (blood loss or chronic disease)
• CXR: bilateral alveolar infiltrates (pulmonary haemorrhage)
• ABG: hypoxia if pulmonary involvement
• Carbon monoxide transfer factor (KCO): raised (trapped CO in haemoglobin within alveoli) – most sensitive marker of alveolar haemorrhage

Renal Biopsy

• Urgent (within 24 hours)
• LM: crescentic GN (>50% crescents)
• IF: linear IgG along GBM – pathognomonic
• IF may also show linear C3
• EM: no electron-dense deposits (unlike immune complex disease)
• Proportion of fibrous vs cellular crescents: key prognostic indicator

Emergency Treatment (Start Immediately)

Triple therapy:

1. Plasma exchange: 4L exchanges daily or alternate days for 14 sessions (removes circulating anti-GBM antibodies); replace with 5% albumin (FFP if recent biopsy or active haemorrhage)
2. Cyclophosphamide: 2-3mg/kg/day PO for 3 months (prevents new antibody production)
3. Prednisolone: 1mg/kg/day (max 60mg) tapering over 6 months; often preceded by IV methylprednisolone 500mg-1g × 3 days

Supportive

• Dialysis: if required for fluid overload, hyperkalaemia, uraemia
• Mechanical ventilation: if massive pulmonary haemorrhage
• Smoking cessation: essential
• PCP prophylaxis: co-trimoxazole during immunosuppression

Duration and Monitoring

• Treatment typically 3-6 months total (shorter than ANCA vasculitis)
• Monitor anti-GBM titre: aim for negative
• Relapse is very rare (<5%); long-term maintenance NOT required

Transplantation

• Can be considered once anti-GBM antibodies negative for >6 months
• Recurrence in transplant: very rare (<5%)
• Wait at least 12 months after antibodies clear

Referral Criteria

• All cases → urgent nephrology (same day)
• Pulmonary haemorrhage → ICU
• Dialysis-dependent → renal team

• Overall renal survival: 30-40% at 1 year
• Creatinine <500 µmol/L at presentation: 80-90% renal recovery
• Creatinine >500 µmol/L and dialysis-dependent: <10% renal recovery (particularly if 100% crescents on biopsy)
• Patient survival: >90% at 1 year with treatment
• Pulmonary haemorrhage mortality: ~10% with treatment; higher if massive
• Double-positive (anti-GBM + ANCA): better renal prognosis than anti-GBM alone (30-40% more likely to recover renal function); but higher relapse risk (ANCA-related)
• Relapse: very rare (<5%) – one of the few advantages of this disease vs ANCA vasculitis

Anti-GBM Disease vs ANCA Vasculitis

Prognostic Factors