18th February 2025

Anti-GBM (Goodpasture) disease

Anti-glomerular basement membrane (GBM) disease is a small-vessel vasculitis associated with anti-GBM antibodies (against type IV collagen). It is rare, with peak incidences in the 3rd and 6-7th decades. The classic presentation is with large volume haemoptysis and rapidly progressive glomerulonephritis, although younger patients are more likely to present with pulmonary haemorrhage and older patients with isolated glomerulonephritis.

It is thought that a triggering stimulus is needed on a background of genetic predisposition (HLA-DR15 and HLA-DR4 are associated). Stimuli include drugs such as alemtuzumab, cocaine use, infections including influenza, smoking and extracorporeal shockwave lithotripsy for ureteric stones.

Clinical features of anti-GBM disease

The most common pulmonary feature is alveolar haemorrhage. Other features include:

• Systemic symptoms such as malaise, weight loss, fever or arthralgia for typically only a few weeks
• Iron-deficiency anaemia due to prolonged pulmonary bleeding
• Rapidly progressive glomerulonephritis causing nephritic syndrome and proteinuria (not usually in the nephrotic range)

Investigations in anti-GBM disease

Diagnosis of anti-GBM disease requires demonstration of anti-GBM antibodies either in the serum or the kidney.

ANCA testing should be performed in all patients suspected of anti-GBM disease, as the presence of both anti-GBM and ANCA antibodies supports a diagnosis of double-positive anti-GBM and ANCA-associated disease. This requires aggressive early treatment of anti-GBM disease and maintenance of immunosuppression for ANCA-associated vasculitis.

Other investigations include:

• Urine dipstick and microscopy to assess for nephritic syndrome
• Full blood count, liver function tests, urea and electrolytes, clotting +/- group and save depending on presence of pulmonary haemorrhage
• Kidney biopsy should be performed without delay unless contraindicated
• Serum assay for anti-GBM antibodies if kidney biopsy cannot be performed or will be delayed
• Bronchoalveolar lavage is the gold standard to diagnose pulmonary haemorrhage
• Alveolar haemorrhage may be seen on chest X-ray (patchy or diffuse opacities) or CT (ground-glass or consolidative opacities)
• Pulmonary function testing is not routinely performed but may show increased carbon monoxide diffusing capacity (DLCO)

Management of anti-GBM disease

The standard treatment is urgent plasmapheresis to rapidly remove culprit antibodies and subsequent cyclophosphamide and glucocorticoid to inhibit autoantibody production and resolve inflammation. Plasmapheresis can be initiated before antibody testing comes back if clinical suspicion of the disease is high. Rituximab and mycophenolate have emerging data as agents for induction of remission.

A conservative approach may be appropriate in patients without alveolar haemorrhage (i.e. only renal involvement) but needing dialysis at presentation. This is because their kidneys are likely fully and permanently damaged already (as evidenced by their need for dialysis) and there is a low probability of recovery of kidney function despite plasmapheresis with immunosuppression. If subsequent renal biopsy shows 100% crescents, this is even more reason to continue a conservative approach as the chance of renal recovery is low. A short trial of treatment could be considered if patients are particularly young and able to tolerate aggressive treatment, if the presentation is very acute and thus irreversible damage is less predictable, or if renal biopsy shows only focal crescents or evidence of concurrent ANCA-associated vasculitis.