Anti-GBM disease (Goodpasture's disease): symptoms, diagnosis and treatment

GBM stands for glomerular basement membrane, a thin layer of tissue in the filtering units of the kidneys (the glomeruli). Vasculitis UK explains that anti-GBM disease occurs when the body's immune system attacks the lining, known as the basement membrane, of the small blood vessels in the kidneys and lungs. It is a form of vasculitis, which means inflammation of blood vessels.

The condition is also called Goodpasture's disease. Patient.info uses the term Goodpasture's syndrome for the combination of acute glomerulonephritis (inflamed kidney filters) and bleeding into the lungs (pulmonary alveolar haemorrhage), and notes that anti-GBM antibodies are the essential feature of the disease.

It is not currently known why the immune system does this. Vasculitis UK says people with a particular tissue type seem to be at greater risk, and that lung involvement is more common in cigarette smokers and smoking may also be a trigger. Patient.info lists exposure to organic solvents or hydrocarbons, smoking, infection such as influenza and exposure to metal dusts as possible risk factors.

Vasculitis UK says most people with anti-GBM disease have kidney involvement and that about 50 per cent also have lung disease. Isolated lung disease is very rare. Kidney involvement may not cause symptoms at first, although blood and protein may be detected in the urine.

• Kidney symptoms as the disease progresses: tiredness, poor appetite, decreased urine production, breathlessness and leg swelling.

• Lung symptoms: severe breathlessness, a dry cough or coughing up blood.

• Blood in the urine (haematuria), which Patient.info lists among the presenting features, with pallor from anaemia in some cases.

• Patient.info also lists chills, fever, nausea and vomiting, weight loss and chest pain among symptoms.

Coughing up blood, severe breathlessness, passing very little urine or becoming rapidly unwell with swelling and tiredness are reasons to seek urgent medical help. In the UK that means NHS 111 or an urgent GP appointment if you are unsure, and 999 or A&E if you are struggling to breathe or coughing up significant amounts of blood.

Patient.info describes the condition as typically presenting as acute kidney injury caused by a rapidly progressive glomerulonephritis, with or without pulmonary haemorrhage that may be life-threatening. Vasculitis UK stresses that it is important to make the diagnosis rapidly because treatment is more likely to be effective when started early in the disease.

Vasculitis UK says the diagnosis usually relies on a blood test to identify anti-GBM antibodies. A kidney biopsy, in which a small sample of kidney tissue is taken with a needle, is often required to show that the kidneys are involved, and can confirm the diagnosis by showing deposits of anti-GBM antibodies in the kidney. Other tests, such as X-rays or CT scans, are often used to show whether the lungs are involved.

Patient.info adds that urine tests typically show features of glomerulonephritis, that blood tests assess kidney function and look for anaemia, and that tests for ANCA antibodies are done because they may be present as well. It notes that renal biopsy is not required if anti-GBM antibodies are present.

Vasculitis UK explains that some people are found to have ANCA, an antibody normally associated with other small-vessel vasculitis such as granulomatosis with polyangiitis and microscopic polyangiitis. These so-called double-positive patients receive initial treatment as for anti-GBM disease, including plasma exchange, but are at risk of future relapses linked to ANCA and so continue longer-term maintenance treatment.

Vasculitis UK says treatment requires plasma exchange, a process using a machine to remove anti-GBM antibodies from the bloodstream, often done daily for 2 weeks. In addition, immunosuppressive drugs such as steroids and cyclophosphamide are used to suppress inflammation and stop further antibody production. Rituximab is sometimes used as an additional or alternative treatment to cyclophosphamide. Treatment usually continues for 6 months after the diagnosis is made.

Patient.info says the aim is to rapidly remove the harmful autoantibody, typically with plasma exchange, along with steroids and cytotoxic therapy. It says that in the acute phase, assisted ventilation and haemodialysis are often required, and that end-stage kidney disease can be managed by long-term haemodialysis or kidney transplantation.

Vasculitis UK also mentions imlifidase, an enzyme that digests the antibodies, which has shown promise and was being tested in an international trial that included some UK hospitals. It said that until the results are known it is not available as a routine treatment.

Vasculitis UK says that when treatment is started promptly, before the need for dialysis, the majority of patients recover to have normal kidney and lung function. People already on dialysis are unlikely to recover kidney function. Patient.info says that, with aggressive therapy, one-year survival is 70 to 90%, and that independent kidney function is maintained at 1 year in more than 80% of patients who do not need kidney replacement therapy at presentation.

Relapse is very rare. Vasculitis UK says that, unlike other forms of vasculitis, anti-GBM disease does not usually need long-term treatment, and that smoking is thought to be a possible trigger for relapse and should be avoided. For those who remain on dialysis, transplantation is possible once anti-GBM antibodies are undetectable, and recurrence in a transplanted kidney is very rare.

Patient.info lists a recognised complication of immunosuppressive treatment: infection with the organism Pneumocystis jirovecii, for which preventive treatment may be used. Questions about infection risk and what to do if you feel unwell during treatment are worth raising with the renal team.

Vasculitis UK describes the condition as a form of vasculitis affecting the kidneys and lungs, and the treatments it lists (plasma exchange, steroids, cyclophosphamide or rituximab) are specialist treatments. Patient.info says that in the acute phase assisted ventilation and haemodialysis are often required. In practice this means care is led by a specialist kidney team in hospital, and the diagnosis is usually made as an emergency or urgent referral rather than through routine outpatient waiting lists. Ask the team who your named contact is and what follow-up blood tests are planned.