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 inflamed 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 usually develops 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. Some people experience lots of swelling from the very beginning of the disease, and 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
  • Frothy urine
  • Elevated fat levels in the blood (hyperlipidemia)
  • Increased protein levels in the urine (proteinuria)
  • Decreased protein levels in the blood, particularly of the protein albumin

When to see a doctor

If you have blood in your urine, persistent swelling in your legs and ankles, or increased blood pressure, make an appointment to see a doctor.

In a majority of cases of membranous nephropathy, evidence of autoimmune activity can be found. Your body's immune system mistakes some of your own tissues as foreign and attacks them with autoantibodies. These autoantibodies can damage your kidney's filtering systems (glomeruli).

Sometimes membranous nephropathy is brought on by other causes, notably:

  • 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 can lead to nephrotic syndrome — a cluster of signs and symptoms that affect your kidneys' filtering ability.
  • 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.

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?

To diagnose membranous nephropathy, your doctor may start with a detailed medical history and a physical exam. Your doctor may also recommend certain tests to identify possible causes and to determine how well your kidneys are working. These tests might include:

  • Urine tests. You may be asked to provide a urine sample so that your doctor can determine the amount of protein present in your urine.
  • Blood tests. From a sample of your blood, your doctor can test your cholesterol and triglyceride levels to see if they're elevated. Your doctor may also check your kidney function with a creatinine blood test. Fasting blood sugar and glycosylated hemoglobin tests check for diabetes. Other blood tests may reveal autoimmune diseases or infection with viruses, such as hepatitis B or hepatitis 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. The ANA test checks a sample of your blood for the presence of antinuclear antibodies, substances which attack your body's own tissues. High levels of antinuclear antibodies indicate an autoimmune disease.
  • Imaging exam. An ultrasound or computerized tomography (CT) scan allows your doctor to see the structure of your kidneys and urinary tract.
  • Kidney biopsy. In this procedure, your doctor removes a small piece of your kidney to examine under a microscope and identify what type of kidney disease you have. Kidney biopsy can also assess how much kidney damage has occurred and evaluate the effectiveness of treatment.

In some cases, membranous nephropathy occurs without any noticeable symptoms, and your doctor may discover the condition when the results of a routine urine test (urinalysis) show elevated protein levels in your urine (proteinuria).

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

In cases where membranous nephropathy is caused by a medication or another disease — such as a cancerous tumor — 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 with conservative measures, including:

  • Controlling blood pressure with medications that block the angiotensin II system, such as angiotensin-converting enzyme (ACE) inhibitors
  • Decreasing swelling (edema) with water pills (diuretics), which help remove sodium and water from your blood
  • Controlling cholesterol levels with statin medications
  • Decreasing blood clot risk with an anticoagulant medication
  • Reducing the amount of salt in your diet

Up to 30 percent of people with membranous nephropathy have a complete resolution of symptoms (remission) after five years without any treatment, and 25 to 40 percent have a partial remission. Doctors generally prefer to avoid using strong drugs — and their potential 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 greater the protein level, the greater the risk to your health:

  • Moderate risk. With membranous nephropathy, you're considered at moderate risk of advanced kidney disease if your urine protein level stays between 4 and 8 grams a day with a blood creatinine level at normal or near normal during six months of observation. About half the people with these signs develop serious kidney disease over five years.
  • High risk. With membranous nephropathy, you're considered at high risk of advanced kidney disease if your urine protein level is persistently greater than 8 grams a day for three months or if your kidney function is below normal or falls below normal during the observation period. About 3 in 4 people with these signs have a high risk of progressing to serious kidney disease over five years.

For those at moderate to high risk of developing advanced kidney disease, treatment of membranous nephropathy might include:

  • Medications to suppress your immune system. If your proteinuria is getting worse, your doctor may prescribe a combination of a corticosteroid medication with a chemotherapy drug to suppress your immune system. Alternatively, a type of drug called a calcineurin inhibitor might be given if you can't tolerate or choose not to take a chemotherapy drug.

    These medications can effectively reduce urine protein levels and stop the progress toward kidney failure. But the medications have significant side effects, they don't help everyone, and symptoms return for many people after treatment ends. Some of the side effects of chemotherapy drugs — such as risk of bladder cancer, leukemia and infertility — may occur many years after taking the drug.

    If you don't respond to a first course of immunosuppressive therapy, or you have a relapse, you may benefit from a second course of treatment.

  • Rituximab (Rituxan). Rituximab has shown effectiveness in people who haven't benefited from immunosuppressive therapy. The drug kills B cells in the immune system — the cells that produce antibodies that damage the glomeruli. However, use of this drug is still experimental and rituximab is expensive and not generally covered by insurance.

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
  • Experience. Doctors at Mayo Clinic treat more than 200 people each year who have membranous nephropathy.
  • Expertise. The large number of kidney specialists (nephrologists) at Mayo Clinic allows some doctors to specialize and become skilled at specific aspects of kidney medicine, including glomerular diseases such as membranous nephropathy. Kidney specialists are experts at kidney biopsies and have an outstanding track record for safety. Mayo pathologists are world experts in interpreting biopsies.
  • Access to the latest knowledge. Mayo Clinic is on the forefront of testing antibodies that may be causing membranous nephropathy and new therapies to counteract these antibodies. By participating in clinical trials, you can get access to experimental treatments and help shape the course of future therapy for others.
  • Teamwork. Kidney specialists work with hypertension, transplant and tissue analysis specialists to accurately diagnose your disease and develop the best treatment plan.
  • Coordinated care. Mayo doctors work closely with your local doctor to coordinate treatment and follow-up care.

Mayo Clinic in Rochester, Minn., ranks #1 for kidney disorders in the U.S. News & World Report Best Hospitals rankings. Mayo Clinic in Scottsdale, Ariz., is ranked among the Best Hospitals for kidney disorders, and Mayo Clinic in Jacksonville, Fla., is ranked high performing for kidney disorders by U.S. News & World Report.

At Mayo Clinic, we assemble a team of specialists who take the time to listen and thoroughly understand your health issues and concerns. We tailor the care you receive to your personal health care needs. You can trust our specialists to collaborate and offer you the best possible outcomes, safety and service.

Mayo Clinic is a not-for-profit medical institution that reinvests all earnings into improving medical practice, research and education. We're constantly involved in innovation and medical research, finding solutions to improve your care and quality of life. Your doctor or someone on your medical team is likely involved in research related to your condition.

Our patients tell us that the quality of their interactions, our attention to detail and the efficiency of their visits mean health care — and trusted answers — like they've never experienced.

Why Choose Mayo Clinic

What Sets Mayo Clinic Apart

Mayo Clinic is at the forefront of diagnosing membranous nephropathy. Specialists at Mayo Clinic will soon offer testing for certain immune system substances known as anti-PLA2R antibodies. Anti-PLA2R antibodies are present in the blood of about 75 percent of people with membranous nephropathy.

Monitoring anti-PLA2R antibodies can help guide treatment decisions and check response to therapy in people with membranous nephropathy.

Mayo Clinic doctors continually investigate possible new approaches in the treatment of membranous nephropathy. Your treatment of membranous nephropathy could include participation in a clinical trial, if you qualify. Currently underway is a randomized, controlled trial studying the effectiveness of rituximab (Rituxan) versus cyclosporine, a calcineurin inhibitor, in treating membranous nephropathy. Your doctor can assess whether or not you might be a candidate for such a clinical trial.

Mayo Clinic works with hundreds of insurance companies and is an in-network provider for millions of people. In most cases, Mayo Clinic doesn't require a physician referral. Some insurers require referrals or may have additional requirements for certain medical care. All appointments are prioritized on the basis of medical need.

At Mayo Clinic's campus in Arizona, specialists in nephrology and hypertension care for people who have membranous nephropathy.

For appointments or more information, call the Central Appointment Office at 800-446-2279 (toll-free) 8 a.m. to 5 p.m. Mountain Standard Time, Monday through Friday or complete an online appointment request form.

At Mayo Clinic's campus in Florida, specialists in nephrology and hypertension care for people who have membranous nephropathy.

For appointments or more information, call the Central Appointment Office at 904-953-0853 8 a.m. to 5 p.m. Eastern time, Monday through Friday or complete an online appointment request form.

At Mayo Clinic's campus in Minnesota, specialists in nephrology and hypertension care for people who have membranous nephropathy. Doctors in the Glomerular Disease/Renal Parenchymal Clinic provide comprehensive care in diagnosing and treating disorders that affect the kidney's filtering units (glomeruli), including membranous nephropathy.

For appointments or more information, call the Central Appointment Office at 507-538-3270 7 a.m. to 6 p.m. Central time, Monday through Friday or complete an online appointment request form.

See information on patient services at the three Mayo Clinic locations, including transportation options and lodging.

The Mayo Nephrology Collaborative Group (MNCG) develops and conducts studies of renal parenchymal diseases, including membranous nephropathy. The MNCG is a consortium of nephrologists from Mayo Clinic campuses in Minnesota, Florida and Arizona and from other centers across the United States.

Mayo Clinic has conducted clinical studies evaluating the feasibility and effectiveness of rituximab (Rituxan) in treating membranous nephropathy. A randomized trial comparing the drug with the calcineurin inhibitor cyclosporine is underway. Mayo researchers are also studying the role of a variety of antibodies in membranous nephropathy.

Mayo is also evaluating the use of adrenocorticotropic hormone (ACTH) in the treatment of membranous nephropathy. Recent European studies have shown that treatment with synthetic ACTH is highly effective in reducing proteinuria with minimal side effects in people who have membranous nephropathy. Mayo is looking to confirm these findings in U.S. patients.

See a list of publications on membranous nephropathy by Mayo doctors on PubMed.

Oct. 21, 2014