Glomerulonephritis Membranous

Membranous glomerulonephritis is a kidney disease where your immune system mistakenly attacks the tiny filters in your kidneys, causing protein to leak into your urine and potentially leading to serious complications if left untreated.

membranous nephropathy, membranous glomerulopathy, membranous nephritis, extramembranous glomerulonephritis

Table of contents

• What Is Membranous Glomerulonephritis?
• Types of the Condition
• How Common Is This Condition?
• What Causes Membranous Glomerulonephritis?
• Signs and Symptoms
• Possible Complications
• How Is It Diagnosed?
• Treatment Options
• What to Expect

What Is Membranous Glomerulonephritis?

Membranous glomerulonephritis is a condition that affects your kidneys’ ability to filter waste from your blood. Your kidneys contain thousands of tiny filtering units called glomeruli (the singular is glomerulus). These filters are responsible for cleaning waste products from your blood and making urine^[1].

In membranous glomerulonephritis, your immune system attacks these glomeruli, causing them to become inflamed and damaged. When this happens, the filters in your kidneys become thicker and more permeable than they should be. This means they start letting through substances that should stay in your blood, particularly proteins^[2].

The condition can develop suddenly or get worse slowly over time. Many people have membranous glomerulonephritis for several years without knowing it because they don’t notice any symptoms^[1].

Types of the Condition

There are two main types of membranous glomerulonephritis, classified based on what causes the disease^[1][2].

Primary membranous nephropathy (also called idiopathic) directly affects your kidneys. This type is usually caused by an autoimmune condition, meaning your body’s defense system attacks healthy cells by mistake. Between 75% and 80% of people with membranous glomerulonephritis have this type. In most cases, the immune system produces antibodies (proteins that normally fight infections) against a protein called phospholipase A2 receptor (PLA2R), which is found on kidney cells. About 70% to 80% of primary cases involve anti-PLA2R antibodies^[2][4].

Secondary membranous nephropathy happens when another health condition or treatment affects your kidneys. About 20% to 25% of people have this type. The kidney damage is a side effect of the other condition rather than a disease targeting the kidneys directly^[2].

How Common Is This Condition?

Membranous glomerulonephritis is rare. Only about 1 in every 5,000 people has this condition^[1]. It is one of the most common causes of nephrotic syndrome (a group of symptoms including protein in the urine and swelling) in adults^[2][4].

The condition is more common in men than women and typically affects people aged 50 to 60. It rarely occurs in children^[1].

What Causes Membranous Glomerulonephritis?

The most common cause of primary membranous glomerulonephritis is an autoimmune process. Your immune system makes antibodies to proteins found in your kidney cells, particularly the PLA2R protein. Instead of fighting an infection, these antibodies attack healthy kidney cells. This stops your kidneys from filtering properly and allows proteins to leak into your urine^[1][4].

Several other autoantibodies have been discovered in recent years that can cause the disease. These include antibodies against thrombospondin type 1 domain-containing 7A (THSD7A), neural epidermal growth factor-like 1 protein (NELL-1), and exostosin (EXT1/EXT2)^[2][3].

Secondary membranous glomerulonephritis develops as a result of other medical conditions or exposures. You’re more likely to develop the secondary form if you have^[1][2][5]:

• Autoimmune diseases such as lupus, rheumatoid arthritis, or Graves’ disease
• Infections including hepatitis B, hepatitis C, malaria, or syphilis
• Certain types of cancer, especially lung and colon cancer, or melanoma
• Exposure to toxins such as mercury or gold
• Use of certain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), penicillamine, or probenecid
• A history of kidney or bone marrow transplant

Signs and Symptoms

The main symptoms of membranous glomerulonephritis come from excess protein in your urine due to kidney damage. This leads to water retention and other problems. Together, these symptoms are called nephrotic syndrome^[1][2].

Many people have no noticeable symptoms at first. When symptoms do appear, they may include^[1][5][7]:

• Edema (swelling) in the hands, feet, ankles, and face
• Foamy-looking urine caused by high levels of protein in the urine (proteinuria)
• Fatigue and weakness
• Weight gain, usually from water retention
• Poor appetite
• More frequent urination, especially at night
• Blood in the urine (hematuria)
• High blood pressure
• Trouble breathing or shortness of breath

The damage to your kidneys causes protein to filter from your blood into your urine. Your body needs protein, and losing too much leads to low protein levels in your blood. This causes fluid to leak out of blood vessels into your tissues, resulting in swelling^[1].

Possible Complications

If membranous glomerulonephritis is not properly managed, it can lead to serious health problems^[1][7]:

• High cholesterol (higher than normal levels of fat in your blood)
• High blood pressure
• Severe swelling throughout the body
• Chronic kidney disease
• Kidney failure, which may require dialysis or transplant
• Deep vein thrombosis (DVT), which are blood clots that form in the legs
• Pulmonary embolism (PE), which occurs when blood clots travel to the lungs

The risk of blood clots increases significantly when blood protein levels drop below certain thresholds. Research shows that the risk of developing blood clots increases nearly 4 times when serum albumin falls below 2.8 grams per deciliter^[8].

How Is It Diagnosed?

If you have symptoms of nephrotic syndrome such as protein in your urine, swelling, or decreased kidney function, your doctor may refer you to a nephrologist. This is a healthcare provider who specializes in diseases and conditions of the kidneys^[1].

The diagnostic process typically includes several steps^[5][12]:

Physical examination: Your doctor will check for signs of swelling, measure your blood pressure, and assess your overall health.

Urine tests: A urine sample is collected to check for protein (proteinuria) and blood (hematuria) in your urine. Your doctor may also request a urine protein to creatinine ratio test.

Blood tests: Blood samples are taken to measure kidney function, including serum creatinine, blood urea nitrogen, and creatinine clearance. Tests also check for low albumin levels, high cholesterol, and other abnormalities. Additional blood tests may look for specific antibodies like anti-PLA2R or anti-THSD7A, which help determine if you have primary membranous nephropathy^[3][4].

Tests to identify secondary causes: If secondary membranous nephropathy is suspected, your doctor may order tests for hepatitis B and C, syphilis, malaria, autoimmune markers, and complement levels^[5].

Kidney biopsy: A small piece of kidney tissue is removed through a needle and examined under a microscope. This is the definitive test to confirm the diagnosis and assess the severity of kidney damage. However, in some cases with high anti-PLA2R antibody levels and typical symptoms, a biopsy may be avoided^[3][5].

Imaging tests: A kidney ultrasound may be performed to examine the kidneys’ structure.

Treatment Options

Treatment for membranous glomerulonephritis depends on whether you have the primary or secondary form, the severity of your symptoms, and your risk of kidney damage^[1][8].

Treating Secondary Causes

If you have secondary membranous nephropathy, successfully treating the underlying condition may cure the kidney disease. For example, antiviral therapy may help if the condition is caused by hepatitis B or C^[8].

Managing Symptoms

All patients, regardless of type, receive treatments to manage symptoms and protect kidney function^[5][8]:

• Blood pressure control: Medications called ACE inhibitors (angiotensin-converting enzyme inhibitors) or ARBs (angiotensin receptor blockers) help lower blood pressure and reduce protein loss in urine
• Diuretics: These medications help control swelling by removing excess fluid from the body. Loop diuretics are most commonly used
• Dietary changes: A low-sodium (salt) and low-protein diet may be recommended. Reducing salt helps control swelling and blood pressure
• Cholesterol management: Statins are prescribed to treat high cholesterol, which is common in people with this condition
• Lifestyle modifications: Stopping smoking, maintaining a healthy diet, and regular exercise can help manage the condition

Immunosuppressive Therapy

For primary membranous nephropathy, treatment with medicines that suppress the immune system may be needed if you are at moderate to high risk of kidney damage. This includes people with increased creatinine levels, progressive disease, or severe symptoms^[8][9].

The main treatment options include:

Rituximab: This is now considered the first-line treatment. It is a monoclonal antibody that targets B lymphocytes (a type of immune cell). Studies show it is effective in reducing antibody levels and achieving remission^[8][9].

Corticosteroids combined with alkylating agents: This traditional approach uses steroids like prednisolone together with either cyclophosphamide or chlorambucil. However, this is now mainly reserved for patients at very high risk of kidney failure or those who cannot take rituximab^[8].

Calcineurin inhibitors: Medications such as cyclosporine or tacrolimus may be used as an alternative^[8].

Other Considerations

Regular monitoring and follow-up visits are necessary to track kidney function, protein levels in urine, and adjust treatment as needed^[5].

Anticoagulation (blood-thinning medication) may be considered for patients at high risk of blood clots, particularly those with very low albumin levels^[8].

Vaccines, including seasonal flu and pneumonia vaccines, are recommended because the condition and its treatments can make you more vulnerable to infections^[18].

Advanced Kidney Disease

If membranous glomerulonephritis progresses to end-stage kidney disease (kidney failure), you may need^[1]:

• Dialysis: A treatment that takes over some of the kidney’s work by removing waste products from your blood
• Kidney transplant: Surgery to replace your damaged kidney with a healthy kidney from a donor

What to Expect

The outlook for people with membranous glomerulonephritis varies widely. Some people experience spontaneous remission, meaning the condition improves on its own without treatment. Others have persistent protein in their urine with stable kidney function, while some may progress to kidney failure^[4].

With appropriate treatment, many patients can achieve remission and prevent kidney damage. Tracking anti-PLA2R antibody levels over time helps doctors predict the risk of disease progression and the chance of spontaneous remission^[3].

Regular monitoring is essential. Your healthcare team will check your kidney function, protein levels in urine, blood pressure, and overall health at scheduled intervals to adjust treatment as needed^[5].