Anti-glomerular basement membrane disease

Goodpasture’s disease, Goodpasture disease, Anti-GBM disease

Anti-glomerular basement membrane disease is a rare and life-threatening condition where your immune system mistakenly attacks your kidneys and lungs, potentially leading to kidney failure and severe breathing problems within weeks if left untreated.

Table of contents

• What is anti-GBM disease?
• How common is the disease?
• Who is more likely to develop this disease?
• What are the symptoms?
• What causes the disease?
• What complications can occur?
• How is it diagnosed?
• How is it treated?

What is anti-GBM disease?

Anti-glomerular basement membrane disease, often called anti-GBM disease, is a disorder in which your body’s immune system (the system that normally protects you from infections) creates harmful antibodies (proteins that fight infection) that attack your kidneys and lungs^[1]. This happens because your immune system mistakenly attacks collagen, a protein that helps make up your skin, muscles, and the structures in your kidneys and lungs, treating it as if it were a foreign invader^[3].

The disease specifically targets the glomerular basement membrane (GBM) in your kidneys. The GBM is part of tiny blood vessels called glomeruli that filter waste and extra fluid from your blood^[3]. The antibodies can also attack similar structures in the air sacs of your lungs.

As a result of this attack, you may develop one or both of these serious conditions: glomerulonephritis, which is inflammation of the glomeruli in your kidneys, and bleeding in your lungs^[1]. If left untreated, anti-GBM disease can quickly get worse and may lead to kidney failure (when your kidneys stop working) and death^[1].

Another related term is Goodpasture syndrome, which refers specifically to the combination of kidney inflammation and lung bleeding. When a patient has both lung and kidney problems together, doctors often use this term^[1]. However, anti-GBM disease is the broader medical name for this condition.

How common is the disease?

Anti-GBM disease is very rare. Healthcare experts report only about 1 in 1 million new cases being reported per year^[1]. In fact, fewer than two new cases per 1 million people occur yearly^[3]. Because it is so uncommon, many doctors who are not specialists in kidney disease may not be familiar with it, which can sometimes lead to delays in diagnosis.

Who is more likely to develop this disease?

Anti-GBM disease can affect people of all ages, but it most often affects men in their 20s and women in their 60s^[1]. However, the condition can occur at any age. The disease more often affects people early in life, particularly teens to people in their 30s, and then again in those in their 60s and 70s^[3].

The condition can occur in children, but this is extremely rare^[1].

You may be more likely to develop anti-GBM disease if you smoke, inhale cocaine, or have exposure to metal dust and hydrocarbon chemicals like methane or propane^[3]. Sometimes, the disease can develop after an infection, like a cold or the flu^[3]. Studies have shown a strong association with a specific genetic marker called human leukocyte antigen (HLA) DR15, which suggests that the genes you inherit from your biological parents may play a role^[3].

What are the symptoms?

Anti-GBM disease most often starts with general symptoms that may appear vague at first. These early symptoms include feeling very tired (fatigue), weakness, anemia (low red blood cell counts), general body discomfort or pain, nausea, and vomiting^[1]. These symptoms may appear before or along with symptoms specifically related to lung and kidney problems.

Because anti-GBM disease affects both the lungs and kidneys, symptoms can relate to either or both organs. Lung-related symptoms usually appear first and may include coughing up blood, dry cough, shortness of breath (dyspnea), chest pain, a rattling lung sound when you breathe in, nosebleeds, and pale skin^[1][3].

Symptoms related to kidney problems may include pink or cola-colored urine from blood in your urine (called hematuria), swelling in your feet and legs (called edema), high blood pressure (hypertension), foamy urine due to too much protein (proteinuria), peeing less than usual, and a burning sensation when urinating^[1][2][3].

It is important to seek a health care professional’s help right away if you have these symptoms, as the disease can progress rapidly^[1].

What causes the disease?

Researchers don’t fully understand the exact cause of anti-GBM disease^[1]. What is known is that the disease occurs when your immune system mistakenly attacks and destroys healthy body tissue^[2]. In this condition, your body develops substances called anti-glomerular basement membrane antibodies that attack a specific protein called collagen in the tiny air sacs in the lungs and the filtering units of the kidneys^[2].

The antibodies target two specific regions of the collagen structure, designated as EA and EB epitopes, located in a specific part of type IV collagen. These areas are normally hidden within the structure of the basement membrane^[4].

Healthcare providers and medical researchers believe the cause may result from a combination of environmental factors and genes you inherit from your biological parents^[3]. Sometimes the immune system may attack organs or tissues because it mistakes them for viruses or foreign chemicals, particularly after a viral respiratory infection or after breathing in hydrocarbon solvents^[2].

What complications can occur?

If not treated promptly, anti-GBM disease can cause very serious complications. These include severe kidney inflammation, which can quickly lead to kidney failure, and severe bleeding in the lungs, which can cause respiratory failure (when your lungs cannot work properly)^[1].

Untreated, the condition can lead to chronic kidney disease, end-stage kidney disease (when kidneys completely fail), lung failure, and a rapidly worsening form of kidney inflammation called rapidly progressive glomerulonephritis^[2]. Severe lung bleeding is the main cause of death from this disease^[3]. In one out of eight patients, anti-GBM can become fatal during the acute phase, while the majority of patients end up needing dialysis^[14].

Only one in three anti-GBM patients will have preserved kidney function after six months with current standard treatment^[14]. This is why early diagnosis and prompt treatment are critical.

How is it diagnosed?

A healthcare provider will ask about your symptoms and perform a physical exam. During the exam, they may check your blood pressure and listen to your heart and lungs with a stethoscope, potentially hearing abnormal sounds^[2]. The provider may also look for signs of fluid overload and swelling^[2].

Several tests are used to help diagnose anti-GBM disease. Blood tests are performed to measure your estimated glomerular filtration rate (eGFR), which shows how well your kidneys are filtering blood. Blood tests can also detect anti-glomerular basement membrane antibodies, and measure levels of blood urea nitrogen (BUN) and creatinine (serum), which are waste products that build up when kidneys aren’t working properly^[2][3].

Urine tests (urinalysis) are often abnormal and show blood and protein in the urine, along with abnormal red blood cells^[2]. A chest x-ray may be performed to check for lung problems, and arterial blood gas tests may be done to measure oxygen levels in your blood^[2].

In many cases, a kidney biopsy or lung biopsy is performed. This involves taking a small sample of tissue from your kidney or lung to examine under a microscope^[2]. The identification of anti-GBM antibodies in the patient’s serum or tissues is of paramount importance in confirming the diagnosis^[4].

How is it treated?

The main goal of treatment is to remove the harmful antibodies from the blood and stop your immune system from making more of them. Hospitalization is required for prompt diagnosis and treatment, close monitoring, and supportive care^[7]. Patients may initially require intensive care.

Treatment typically includes several approaches used together. Plasmapheresis is a procedure that removes harmful antibodies from your blood to help reduce inflammation in the kidneys and lungs. It works like a type of blood transfusion where blood is filtered through a machine^[2][3]. Therapy usually consists of 14 treatments during 2 to 3 weeks^[7]. Early plasmapheresis removes circulating anti-GBM antibodies and other mediators of inflammation and has been advocated as the treatment of choice^[7].

Corticosteroid medicines, such as prednisone or methylprednisolone pulses, and other drugs that suppress or quiet the immune system are used alongside plasmapheresis^[2]. Concomitant administration of cyclophosphamide and steroids is essential to prevent rebound antibody formation^[7].

Medicines such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) may be given to help control blood pressure^[2]. You may be told to limit your intake of salt and fluids to control swelling, and in some cases, a low-to-moderate protein diet may be recommended^[2].

In some cases, a medication called rituximab, which targets specific immune cells, has been used as an alternative or addition to standard therapy, particularly in refractory or poor-tolerance patients^[7][8]. However, there is insufficient evidence to recommend it as a first-line therapy^[7].

If kidney failure is severe and can no longer be treated by other means, dialysis may be needed. This is a procedure that uses a machine to filter your blood when your kidneys cannot^[2]. A kidney transplant may be done when your kidneys no longer function, but this is not possible in the acute phase and typically becomes an option after about a year^[2][14].

Most patients with lung bleeding respond rapidly to treatment with methylprednisolone pulses and plasma exchange^[7]. Patients with mild kidney disease who do not have lung bleeding may be successfully treated with prednisone alone^[7].

The outlook depends on how early treatment begins. An early diagnosis is very important, as the outlook is much worse if the kidneys are already severely damaged when treatment begins^[2]. Patients with moderate kidney inflammation and those with acute disease are likely to respond to therapy, while patients with advanced disease are unlikely to improve with aggressive treatment and should be spared the risks^[7].