Definition

When the small blood vessels in the kidney become thickened and inflamed, membranous nephropathy occurs. These small blood vessels filter the waste material from the blood. When these blood vessels get infected or thickened proteins leak from the damaged ones into the urine. In many cases, the loss of the proteins causes symptoms known as nephrotic syndrome. If the case is mild, the symptoms can improve on its own, but if the leakage increases, the risk of lasting kidney damage also increases. Unfortunately, in many cases the membranous nephropathy brings to kidney failure. There is no cure for this disease, but successful treatment can make the condition better.

 

Symptoms

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.

 

Causes

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.

 

Risk factors

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

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.

 

Treatment

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.