Anti-GBM Disease

Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune disease caused by autoantibodies to the alpha-3 chain of type IV collagen (NC1 domain), causing crescentic glomerulonephritis with or without pulmonary haemorrhage (Goodpasture syndrome).

• Incidence about 1 per million per year; bimodal peaks (young men aged 20 to 30 with lung involvement; older women aged 60 to 70 with renal-limited disease).
• Associations: HLA-DRB1*15:01, smoking, hydrocarbon exposure, respiratory infection, cocaine inhalation, lithotripsy.
• 10 to 40% have concomitant ANCA (MPO more often).
• Prognosis depends on serum creatinine at presentation: creatinine under 500 µmol/L has over 80% renal survival; dialysis-dependent at presentation recovers in under 10%; 100% crescents with dialysis need rarely recover.
• Relapse is rare (under 5%); recurrence after transplant is uncommon if antibodies undetectable.

• Rapidly progressive renal failure with haematuria, oliguria, oedema, hypertension (may be absent).
• Pulmonary haemorrhage: haemoptysis, dyspnoea, hypoxia, anaemia.
• Systemic features minimal; no purpura or neuropathy unless ANCA overlap.
• Fatigue, pallor from iron deficiency.

• Serum anti-GBM antibodies (ELISA, sensitivity over 95%); ANCA (MPO, PR3) in all.
• Renal biopsy: crescentic GN (often 100% crescents, single-age lesions) with linear IgG along GBM on immunofluorescence.
• Urinalysis: dysmorphic red cells, red cell casts, proteinuria (usually under 3 g/day).
• Chest radiograph and CT: bilateral alveolar opacities; bronchoalveolar lavage with haemosiderin-laden macrophages; raised DLCO during haemorrhage.
• Baseline creatinine, haemoglobin, iron studies.
• Exclude other pulmonary-renal syndromes (ANCA vasculitis, lupus, IgA vasculitis, cryoglobulinaemia, infection).

Begin immediately upon strong clinical suspicion.

• Plasma exchange daily (60 mL/kg, 4 L, 5% albumin) for 14 days or until anti-GBM antibodies undetectable; use fresh frozen plasma for the last 150 to 300 mL of each exchange if pulmonary haemorrhage or recent biopsy.
• Cyclophosphamide 2 mg/kg/day orally (1.5 mg/kg if over 55 years, reduce for renal impairment) for 2 to 3 months, or IV 500 mg/m2.
• Glucocorticoids: methylprednisolone 500 to 1000 mg IV daily for 3 days, then prednisolone 1 mg/kg (maximum 60 to 80 mg) tapered to stop by 6 months.
• Imlifidase 0.25 mg/kg single dose (IgG-cleaving enzyme) in dialysis-dependent patients, with standard therapy.
• Rituximab for refractory disease or contraindication to cyclophosphamide.
• Supportive: dialysis, oxygen and ventilation for haemorrhage, transfusion, Pneumocystis prophylaxis, bone and gastric protection.
• Stop smoking, avoid hydrocarbons.
• Monitor anti-GBM titres weekly until negative, then monthly for 6 months.
• Transplantation after antibody negative for at least 6 months; ANCA double-positive patients need maintenance therapy per ANCA protocol.