• What is Anti-GBM Disease (also known as Goodpasture's Syndrome)?

• Who gets Anti-GBM Disease?

• What are the symptoms?

• How Is Anti-GBM Diagnosed?

• How is Anti-GBM Treated?

• Kidney Transplant in Anti-GBM Disease

• Patient Education Podcasts on Anti-GBM

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 caused by autoantibodies that attack the walls of these blood vessels.

In the kidneys, the capillaries that are attacked are in the glomeruli, which are the tiny clusters of capillaries that filter blood and make urine. These glomerular capillaries have thin membranes in their walls that are the targets of the autoantibodies, which are called anti-glomerular basement membrane (anti-GBM) antibodies. The antibodies are found circulating in the serum and targeted to a very specific basement membrane protein (the α3 chain of type IV collagen). Injury to glomerular capillaries causes bleeding into the urine (hematuria), spillage of blood proteins into the urine (proteinuria), and impaired kidney function.

In the lungs, the capillaries that are attacked are in the thin walls of air sacs (alveoli) where oxygen enters the blood and carbon dioxide exits. Injury to these pulmonary capillaries causes lung hemorrhage and impaired breathing.

Anti-GBM disease that only affects the kidneys is called anti-GBM glomerulonephritis (glomerulo = glomerulus, nephro = kidney, itis = inflammation). 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, which is inflammation (-itis) of capillaries in the alveoli (air sacs) of the lungs. The kidney disease is anti-GBM glomerulonephritis.

In kidney (glomerular) and lung (alveolar) capillaries, the inflammation (attack by white blood cells) is caused by the anti-GBM antibodies binding to a basement membrane protein (type IV collagen) .

Under normal conditions, a layer of cells (endothelial cells) called endothelium, protects the basement membrane from circulating antibodies. However, under circumstances of increased permeability (leakiness) of the endothelium (such as occurs in certain types of lung injury; namely exposures to organic solvents or hydrocarbons, smoking, infection, cocaine inhalation, and metal dusts), the basement membrane becomes more accessible to anti-GBM antibodies allowing them to bind to the vessel wall and cause the inflammation and bleeding that are the hallmarks of this anti-GBM disease.

The drawings below show how anti-GBM antibodies bind to capillary walls and attract and activate white blood cells that release molecular factors that injure the vessel walls.

 

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Who gets Anti-Glomerular Basement Membrane Disease?

Glomerulonephritis due to Anti-GBM antibody disease is rare. The incidence of this disease is reported to be less than 1 case per million persons. It affects mostly young, white men aged 15-35 (M:F 2-9:1), but 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.) .

A number of lines of evidence suggest that genetics may play an important role in this disease. Patient’s with Anti-GBM disease have an increased incidence of the human leukocyte antigen HLA-DR-W15 and individuals with HLA-B7 tend to have a more severe form of nephritis.

 

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What are the symptoms?

• 60-70% pf patients have both pulmonary (lung) and renal (kidney) involvement, which is called Goodpasture’s Syndrome
• 20-40% have only renal involvement, which is called "renal limited" anti-GBM disease
• Hemoptysis (coughing up blood) is the most frequent presenting symptom when the lungs are involved

Other symptoms may include:

• chills and fever
• nausea and vomiting
• weight loss
• chest pain
• Hemorrhage (bleeding) may cause anemia, respiratory failure
• Kidney failure
  

 

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How is Anti-GBM diagnosed?

• A Chest X-ray may be done to look for hemorrhage 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 present 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 evaluate the cause of the pulmonary hemorrhage.
• A lung biopsy and/or kidney biopsy may be required to get a definitive diagnosis.
  

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How is Anti-GBM treated?

Once the diagnosis is confirmed (with the detection of the antibodies in serum and biopsy proven evidence of disease), there are essentially three components to treatment.

REMOVAL OF ANTI-GBM ANTIBODY FROM CIRCULATION BY PLASMAPHERESIS
Plasmapheresis is a procedure that takes the patient’s blood out of the body in small volumes, removes the antibody carrying component, and then the remainder of the blood is returned to the patient. Sometimes a fluid replacement is given back to the patient to replace the component that has been removed.

The number of plasmapharesis treatments can be quite variable depending on patient response. In general, most patients receive between 5-14 treatments – either daily or at some presecribed spacing over 14 to 21 days.

PREVENTION OF FURTHER ANTIBODY PRODUCTION BY IMMUNOSUPPRESSION
Most patients are given “pulse” large dose methylprednisolone by intravenous infusion each day for 3 days. This is a steroid that is quick acting and is used to quickly alter the immune system function and therefore decrease the production of new antibody. This is then followed by daily oral steroid therapy that may go for as long as 3 months (more or less based on disease response to therapy). Cyclophosphamide (Cytoxan®) is the other agent that is most often used with steroid therapy to suppress the production of Anti-GBM antibodies. This can be given orally or by intravenous infusion, but is in general given intravenously in single monthly dose.

AVOIDING OR PREVENTING FUTURE EXPOSURES
Avoiding potential chemical exposures/inhalations that may have caused the disease is important. Immunizations to prevent lung infections may also be useful.

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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.

For some general information about kidney transplant, click here.

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.  Prior to undergoing a kidney transplant, it is recommended that patients wait a minimum of 6 months after treatment for anti-GBM disease is completed.  Once it is certain 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 (occurs in less than 5% of patients).

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