What is Anti-Glomerular Basement Membrane Disease (also known as Goodpasture's Syndrome)?
Anti-GBM disease is the result of injury to small blood vessels (capillaries) in the kidney or lung. This can be caused by autoantibodies that attack the walls of these blood vessels.
In the kidneys, the capillaries that are attacked are in the glomeruli, which filter blood and make urine. These glomerular capillaries have thin membranes in their walls that are the targets of the autoantibodies. These are called anti-glomerular basement membrane (anti-GBM) antibodies. The antibodies are found moving in the serum. The antibodies are connected to a very specific basement membrane protein. Injury to glomerular capillaries causes bleeding into the urine. It can also cause spillage of blood proteins into the urine, and reduced kidney function.
In the lungs, the capillaries that are attacked are in the thin walls of air sacs where oxygen enters the blood and carbon dioxide exits. Injury to these pulmonary capillaries causes lung bleeding and impaired breathing.
Anti-GBM disease that only affects the kidneys is called anti-GBM glomerulonephritis. This is a form of inflammation (-itis), which is injury to tissue caused by white blood cells (leukocytes).
Anti-GBM disease that causes both kidney disease and lung disease is called Goodpasture’s syndrome. The lung disease is anti-GBM alveolar capillaritis. This is inflammation of capillaries in the air sacs of the lungs. The kidney disease is anti-GBM glomerulonephritis.
In kidney (glomerular) and lung (alveolar) capillaries, the attack by white blood cells is caused by the anti-GBM antibodies sticking to a basement membrane protein.
Under normal conditions, a layer of cells called endothelium protects the lower membrane from moving antibodies. However, at times there is increased leakiness of the cell layer. This happens in certain types of lung injury can be caused by exposures to organic solvents or hydrocarbons, smoking, infection, cocaine inhalation, and metal dusts. The lower membrane becomes more accessible to anti-GBM antibodies. This allows them to connect to the vessel wall and cause the swelling and bleeding that signals this anti-GBM disease.
The drawings below show how anti-GBM antibodies attach to capillary walls. They attract and activate white blood cells that attack the vessel walls.
Who gets Anti-Glomerular Basement Membrane Disease?
Glomerulonephritis due to Anti-GBM antibody disease is rare. It occurs in less than 1 case per million persons. It affects mostly young, white men aged 15-35. It also can affect those beginning in the late 50’s. At this age, women are more likely to be affected. It affects both sexes equally and very rarely in children.
Some evidence suggests that genetics may play an important role in this disease.
What are the symptoms?
- 60-70% of patients have both (lung and kidney involvement. This is called Goodpasture’s Syndrome.
- 20-40% have only kidney involvement, which is called "renal limited" anti-GBM disease
- Coughing up blood is the most frequent symptom when the lungs are involved.
Other symptoms may include:
- Chills and fever
- Nausea and vomiting
- Weight loss
- Chest pain
- Bleeding may cause anemia, respiratory failure
- Kidney failure
How is Anti-GBM diagnosed?
- A Chest X-ray may be done to look for bleeding or infection.
- Blood and urine tests can be done to check for kidney involvement.
- A CBC often shows anemia
- A blood test that shows that Anti-Glomerular Basement Membrane Antibodies are in the blood is essential to making the diagnosis.
- As many as one third of patients with Anti-GBM disease will have antineutrophilic cytoplasmic antibodies (ANCA) also present at some time during their disease. This can be done using a blood test.
- Bronchoscopy with cultures may be required to fully investigate the cause of the lung bleeding.
- A lung sample and/or kidney sample may be taken to get a definitive diagnosis.
How is Anti-GBM treated?
Once the diagnosis is confirmed, there are primarily three parts to treatment.
1. The antiGBM antibody is removed from the blood stream by plasmapheresis.
Plasmapheresis is a procedure that takes the patient’s blood out of the body in small amounts. The antibody carrying part of the blood is removed. Then the rest of the blood is returned to the patient. Sometimes fluid is given back to the patient to replace the part of the blood that has been taken away.
The number of plasmapharesis treatments can vary by patient response., Most patients receive between 5-14 treatments. These can be daily or at some approved spacing over 14 to 21 days.
2.) Further antibody production is prevented by immunosuppression.
Most patients are given “pulse” large dose methylprednisolone through a needle inserted into a vein. This is done each day for 3 days. This is a steroid that is quick acting and is used to change the immune system function. This will reduce the production of new antibody. This is then followed by daily oral steroid therapy. The oral steroid may be given for as long as 3 months. The length of time is based on disease response to therapy. Cyclophosphamide (Cytoxan®) is the other agent that is most often used with steroid therapy. This agent is used to suppress the production of Anti-GBM antibodies. It can be given by mouth or by putting a needle in a vein. It is generally delivered through a vein in a single monthly dose.
3.) Future exposures are avoided or prevented.
Avoiding potential chemical exposures that may have caused the disease is important. Shots to prevent lung infections may also be useful.
Kidney Transplant in Anti-GBM Disease
When Anti-Glomerular Basement Membrane (GBM) disease involves the kidneys, it can lead to kidney failure. Fortunately, kidney transplant is a treatment option for these patients.
Will the Anti-GBM Disease come back in my kidney transplant?
Treatment of anti-GBM disease is focused on removing the anti-GBM antibody from the blood. Before having a kidney transplant, it is recommended that patients wait at least 6 months after finishing treatment for anti-GBM disease. Once it is sure that the disease is no longer active, transplant is very safe. The chance that the anti-GBM disease will come back in the kidney is very low. This occurs in less than 5% of patients.