Goodpasture Syndrome (Anti-GBM Disease)

How Goodpasture syndrome works

The kidneys' glomeruli and the lungs' alveoli both have a thin supporting layer called the basement membrane, made partly of type IV collagen. In anti-GBM disease, the immune system makes antibodies against a part of this collagen (the alpha-3 chain). The antibodies bind to the membranes and trigger intense inflammation.

• In the kidneys: a severe, rapidly progressive glomerulonephritis with crescents on biopsy, causing kidney failure over days to weeks.
• In the lungs: bleeding into the air sacs (pulmonary hemorrhage).

About 40 to 60% of people have both kidney and lung involvement; others have kidney disease alone, and a few lung disease alone.

Causes and risk factors

The trigger is not fully understood. Contributing factors include:

• genetic susceptibility, including certain HLA types (such as HLA-DR15)
• lung damage from cigarette smoking, inhaled hydrocarbons or solvents, and cocaine, which may expose the collagen to the immune system; lung bleeding is much more common in smokers
• infections such as influenza in some cases
• kidney injury, lithotripsy or alemtuzumab treatment in rare cases

Some patients also have ANCA antibodies ("double-positive" disease), which overlap with vasculitis such as granulomatosis with polyangiitis.

Symptoms

Lung symptoms

• coughing up blood (hemoptysis), from streaks to large amounts
• shortness of breath and cough
• low oxygen levels

Kidney symptoms

• blood in the urine or dark, cola-colored urine
• foamy urine
• reduced urine output
• swelling of the legs and face
• high blood pressure

General

• fatigue, weakness and pallor from anemia
• nausea, loss of appetite
• fever and joint aches in some

Diagnosis

Speed matters: kidney function can be lost within days.

• Anti-GBM antibody blood test: detects circulating antibodies.
• Kidney biopsy: shows crescentic glomerulonephritis with linear IgG deposits along the basement membrane, the hallmark of the disease.
• ANCA test: to detect overlap with vasculitis.
• Urine tests: blood, red cell casts and protein.
• Blood tests: kidney function (creatinine), blood count for anemia.
• Chest imaging and lung tests: chest X-ray or CT shows bleeding; bronchoscopy may confirm alveolar hemorrhage.

Treatment often starts before the biopsy if suspicion is high.

Treatment

• Plasma exchange (plasmapheresis): removes circulating antibodies from the blood, typically daily or on alternate days for about 2 weeks or until antibodies are gone.
• High-dose corticosteroids: to suppress inflammation.
• Cyclophosphamide: to stop the immune system making new antibodies. Rituximab is an alternative in some cases.
• Dialysis for severe kidney failure.
• Supportive care: oxygen, ventilation for severe lung bleeding, blood transfusions, blood pressure control.
• Stop smoking and avoid inhaled irritants.

Unlike many autoimmune diseases, anti-GBM disease usually does not relapse after successful treatment, so long-term immune suppression is often not needed. Double-positive patients behave more like vasculitis and may relapse.

Outlook

With treatment, survival is high, with most patients alive at 1 year. Kidney outcome depends on how much damage has occurred when treatment starts. People who need dialysis at diagnosis or have a very high proportion of damaged glomeruli often do not recover kidney function and develop kidney failure needing long-term dialysis or a kidney transplant. Transplant is usually delayed until antibodies have been undetectable for at least 6 months.

Frequently asked questions

What is Goodpasture syndrome?

It is a rare autoimmune disease in which antibodies attack the filters of the kidneys and the air sacs of the lungs. It causes rapidly worsening kidney failure and, often, bleeding into the lungs. It is also called anti-GBM disease.

What are the first symptoms of Goodpasture syndrome?

Early symptoms may include tiredness, coughing up blood, shortness of breath, blood in the urine or dark urine, and swelling. Some people have only kidney symptoms. Because it progresses quickly, these symptoms need urgent medical assessment.

Is Goodpasture syndrome curable?

The disease can be controlled and usually does not come back after successful treatment. However, kidney damage that occurs before treatment may be permanent. Early diagnosis and plasma exchange give the best chance of preserving kidney function.

Does smoking cause Goodpasture syndrome?

Smoking does not cause the disease on its own, but it greatly increases the risk of lung bleeding in people who have anti-GBM antibodies. Inhaling solvents or cocaine has a similar effect. Stopping smoking is an important part of treatment.