Membranous nephropathy

Membranous nephropathy is a sometimes silent kidney problem. But it can be serious. Learn the symptoms, treatment and how clinical trials may help.

Membranous nephropathy (MEM-bruh-nus nuh-FROP-uh-thee) occurs when the small blood vessels in the kidney (glomeruli), which filter wastes from the blood, become damaged and thickened. As a result, proteins leak from the damaged blood vessels into the urine (proteinuria). For many, loss of these proteins eventually causes signs and symptoms known as nephrotic syndrome.

In mild cases, membranous nephropathy may get better on its own, without any treatment. As protein leakage increases, so does the risk of long-term kidney damage. In many, the disease ultimately leads to kidney failure. There's no absolute cure for membranous nephropathy, but successful treatment can lead to remission of proteinuria and a good long-term outlook.

Membranous nephropathy may develop gradually, so you may not suspect that anything is wrong. As you lose protein from your blood, swelling in your legs and ankles and weight gain from excess fluid can occur. Many people have lots of swelling from the very beginning of the disease, but others may not have any severe symptoms until they have advanced kidney disease.

Signs and symptoms of membranous nephropathy include:

• Swelling in the legs and ankles
• Weight gain
• Fatigue
• Poor appetite
• Urine that looks foamy
• High cholesterol
• Increased protein in the urine (proteinuria)
• Decreased protein in the blood, particularly albumin

When to see a doctor

Make an appointment with your doctor if you have:

• Blood in your urine
• Swelling in your legs and ankles that doesn't go away
• Increased blood pressure
• Sudden pain between your upper belly and middle back
• Sudden shortness of breath, which could be related to a blood clot complication

Often, membranous nephropathy results from some type of autoimmune activity. Your body's immune system mistakes healthy tissue as foreign and attacks it with substances called autoantibodies. These autoantibodies target certain proteins located in the kidney's filtering systems (glomeruli). This is known as primary membranous nephropathy.

Sometimes membranous nephropathy is brought on by other causes. When this happens, it's called secondary membranous nephropathy. Causes may include:

• Autoimmune disease, such as lupus erythematosus
• Infection with hepatitis B, hepatitis C or syphilis
• Certain medications, such as gold salts and nonsteroidal anti-inflammatory drugs
• Solid cancerous tumors or blood cancers

Membranous nephropathy may also occur along with other kidney diseases, such as diabetic nephropathy and rapidly progressive (crescentic) glomerulonephritis.

Factors that can increase your risk of membranous nephropathy include:

• Having a medical condition that can damage your kidneys. Certain diseases and conditions increase your risk of developing membranous nephropathy, such as lupus and other autoimmune diseases.
• Use of certain medications. Examples of medications that can cause membranous nephropathy include nonsteroidal anti-inflammatory drugs and gold salts.
• Exposure to certain infections. Examples of infections that increase the risk of membranous nephropathy include hepatitis B, hepatitis C and syphilis.
• Genetic background. Certain genetic factors make it more likely that you'll develop membranous nephropathy.

Complications associated with membranous nephropathy include:

• High cholesterol. Levels of cholesterol and triglycerides are often high in people with membranous nephropathy, which greatly increases the risk of heart disease.
• Blood clots. With proteinuria, you may lose proteins that help prevent clotting from your blood into your urine. This makes you more prone to having blood clots develop in deep veins or blood clots that travel to your lungs.
• High blood pressure. Waste buildup in your blood (uremia) and salt retention can raise blood pressure.
• Infections. You're more susceptible to infections when proteinuria causes you to lose immune system proteins (antibodies) that protect you from infection.
• Nephrotic syndrome. High protein levels in the urine, low protein levels in the blood, high blood cholesterol, and swelling (edema) of the eyelids, feet and abdomen occur with this syndrome.
• Acute kidney failure. In cases of severe damage to the kidneys' filtering units (glomeruli), waste products may build up quickly in your blood. You may need emergency dialysis to remove extra fluids and waste from your blood.
• Chronic kidney disease. Your kidneys may gradually lose function over time to the point where you need dialysis or a kidney transplant.

Membranous nephropathy may not cause any signs or symptoms. Sometimes, it's diagnosed when a routine urine test — performed for another health reason — shows that you have high levels of protein in your urine (proteinuria).

If you do have signs or symptoms of protein in the urine, your doctor will ask questions about your medical history and perform a complete physical exam. Your blood pressure will be checked.

Blood, urine and imaging tests can tell your doctor how well your kidneys are working and diagnose membranous nephropathy. They can also help rule out other possible causes of your symptoms.

Tests that may be done include:

• A urine test (urinalysis). You may be asked to provide a urine sample so your doctor can measure how much protein is in your urine.
• Blood tests. A blood sample allows your doctor to check for high cholesterol, high triglycerides, high blood sugar and other factors that can affect the kidneys. A creatinine blood test gives information about your kidney function. Other blood tests can be done to check for autoimmune diseases or viral infections that can cause kidney damage, such as hepatitis B or C.
• Glomerular filtration rate (GFR) test. The GFR test estimates your level of kidney function and can help your doctor determine your stage of kidney disease.
• Antinuclear antibody (ANA) test. This blood tests looks for antinuclear antibodies, substances that attack your body's own tissues. High levels of antinuclear antibodies are a sign of an autoimmune disease.
• Kidney ultrasound or computed tomography (CT). Imaging scans allow your doctor to see the structure of your kidneys and urinary tract.
• Kidney biopsy. A doctor removes a small piece of your kidney to be examined under a microscope. A kidney biopsy is usually needed to confirm the diagnosis. It can tell your doctor the type of kidney disease you have, the amount of kidney damage and what treatments may work best.
• Anti-PLA2R antibody test. This new blood test looks for certain immune substances related to membranous nephropathy. It may help confirm or rule out the disease when a biopsy cannot be done. High levels of these antibodies are a sign of active disease. They've been linked to an increased risk of worsening kidney function.

Treatment of membranous nephropathy focuses on addressing the cause of your disease and relieving your symptoms. There is no certain cure.

However, up to three out of 10 people with membranous nephropathy have their symptoms completely disappear (remission) after five years without any treatment. About 25 to 40 percent have a partial remission.

In cases where membranous nephropathy is caused by a medication or another disease — such as cancer — stopping the medication or controlling the other disease usually improves the condition.

Low risk of advanced kidney disease

With membranous nephropathy, you're considered at low risk of developing advanced kidney disease in the next five years if:

• Your urine protein level remains less than 4 grams a day for six months
• Your blood creatinine level remains in the normal range for six months

If you're at low risk of advanced kidney disease, treatment of membranous nephropathy usually begins by taking the following steps:

• Take blood pressure medication. Doctors typically prescribe an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) to keep your blood pressure under control.
• Decrease swelling (edema). Water pills (diuretics) help remove sodium and water from your blood.
• Control cholesterol. Medications called statins are used to keep your cholesterol in check.
• Lower your risk for blood clots. People with membranous nephropathy are more likely to have deep vein thrombosis or pulmonary embolism. Doctors may prescribe blood-thinners, or anticoagulants, to prevent these dangerous events.
• Cut back on salt. Salt can increase urine protein levels. It also makes your body retain fluid. Check the salt content in foods, drinks and condiments.

Doctors generally prefer to avoid using strong drugs (which can cause significant side effects) early in the course of the disease, when there's a chance that the disease will improve on its own.

Moderate to high risk of advanced kidney disease

Your doctor may recommend more-intensive treatment as the amount of protein in your urine increases. The more protein you have in your urine (proteinuria), the greater the risk to your kidneys and well-being.

In the past, doctors have assessed risk based on the amount of protein in the urine over time:

• Moderate risk. Urine protein level stays between 4 and 8 grams a day and blood creatinine level is at normal or near normal for six months of observation. About half the people with these signs develop serious kidney disease over five years.
• High risk. Urine protein level is persistently greater than 8 grams a day for three months or kidney function is below normal or falls below normal during the observation period. About 3 out of 4 people with these signs are highly likely to develop serious kidney disease over 10 years.

A new approach for assessing risk allows doctors to evaluate antibody levels in the blood along with how much protein is in the urine. This approach also helps doctors determine how you'll respond to therapy.

If you have a moderate to high risk of advanced kidney disease, your doctor may talk to you about these treatments for membranous nephropathy:

• Steroids plus a chemotherapy drug. If your urine protein level keeps rising, your doctor may prescribe a corticosteroid medication with a chemotherapy drug to suppress your immune system. This can lower your urine protein levels and stop the progress toward kidney failure. However, immune suppressing medications don't help everyone. They can also have significant side effects. Some of the side effects of chemotherapy drugs — such as risk of cancer or infertility — may occur many years after taking the drug.
• Cyclosporine. If you don't want to take a chemotherapy drug or cannot tolerate it, cyclosporine (a calcineurin inhibitor drug) is an option.
• Rituximab (Rituxan). Rituximab has helped some people who have not improved with immunosuppressive therapy. Studies suggest it works at least as well as steroid therapy. The medication kills B cells in the immune system — the cells that produce substances, called antibodies, that damage the glomeruli. However, it's expensive and not generally covered by insurance.

Sometimes, the disease comes back after treatment ends. This has happened to people taking any kind of immune suppressants. In some cases, if the first round of treatment doesn't work or you have a relapse, you may benefit from a second round. Talk to your doctor about the best treatment plan for you.

Talk to your doctor about how to reduce your chances of developing kidney disease. Your doctor may suggest that you:

• Have regular checkups
• Follow your prescribed treatment for diabetes or high blood pressure
• Lose excess weight by following a healthy diet and regular exercise program
• Stop smoking, if you are a smoker
• Limit use of over-the-counter pain medications
• Make changes in your diet, such as eating less salt and less protein
• Limit your intake of alcohol

You'll likely start by seeing your primary care doctor if you have signs or symptoms of kidney disease. If lab tests reveal you have kidney damage, you may be referred to a doctor who specializes in kidney problems (nephrologist).

What you can do

To get ready for your appointment, ask if there's anything you need to do ahead of time, such as limit your diet. Ask a friend or family member along to your appointment to help you remember important points later. Then make a list of:

• Your symptoms, including any that seem unrelated to your kidneys or urinary function
• All your medications and doses, including vitamins or other supplements that you take
• Your key medical history, including any other medical conditions
• Questions to ask your doctor.

For membranous nephropathy, some basic questions to ask your doctor include:

• Do I have a problem with my kidneys?
• How badly do my kidneys seem to be affected?
• What kinds of tests do I need?
• What are the possible causes of my condition?
• What treatment approach do you recommend? What are my other treatment options?
• What are the possible side effects of treatment?
• Could my condition go away on its own?
• I have other medical problems. How can I manage them together with this condition?
• Is there anything I can do at home to help with my symptoms?
• What can I expect in the long term?
• If I need a kidney transplant, will that cure me or can the disease come back?
• Do you have any printed materials I can take with me? What websites do you recommend?

Don't hesitate to ask other questions as they occur to you during your appointment.

What to expect from your doctor

Your doctor may ask you questions such as:

• Have you noticed any symptoms?
• When did you first begin experiencing symptoms and how long have they lasted?
• Does anyone in your family have a kidney disease?
• Do you have high blood pressure?
• Do you have diabetes?
• Does anything seem to improve your symptoms? Worsen your symptoms?

Last Updated:

December 24th, 2020