Membranous Nephropathy

What is membranous nephropathy (MN)?

Membranous nephropathy (MN) is a disorder where the body’s immune system attacks the filtering membranes in the kidney. These membranes clean waste products from the blood.

Each kidney has thousands of tiny filtering units called glomeruli. These filtering units are made up of blood vessels so small, they only have three layers:

• Endothelial cells: These cells are part of a single layer of cells on the inside of the blood vessel.
• Podocytes: These cells are in a single layer of cells on the outside of the blood vessel.
• Glomerular basement membrane (GBM): The GBM is a thin membrane in between the two layers of cells

The glomerular basement membrane is so thin that it acts as a filter.

MN can develop very suddenly or slowly get worse over a long time. Some people do not know they have the condition for many years. It is also known as membranous glomerulonephritis.

What happens when one of these layers is damaged?

If inflammation (or anything else) damages any of these three layers, the kidneys cannot work correctly. When the podocyte layer is damaged, it can cause high levels of protein to leak from the kidneys into the urine.

Who is at risk of developing membranous nephropathy (MN)?

People who have higher risk for MN include those who:

• Are older than age 40.
• Are Caucasians. This group has a higher risk than other ethnicities in general, but anyone can develop MN.
• Have a medical condition that can cause damage to the kidneys including cancer and lupus.

What causes membranous nephropathy (MN)?

Most cases of MN are now known to be caused by an antibody to a protein on the podocyte called the phospholipase A2 receptor (PLA2R). In most people with MN, the body’s immune (defense) system makes an antibody (a protein that normally helps fight infections). Instead of targeting an infection, these antibodies attack the podocytes. The podocytes stop retaining the proteins in the blood stream and allow them to leak into the urine. This is called primary MN. Less commonly, MN can be due to other causes (secondary MN), such as:

• Autoimmune disorders (where the body attacks its own cells), including lupus.
• Cancer.
• Certain medicines.
• Hepatitis B virus.
• Parasitic diseases such as malaria.

What are the symptoms of membranous nephropathy (MN)?

The main symptoms of MN are from the loss of protein into the urine because of the damaged podocyte cells. Together, the symptoms of MN are called nephrotic syndrome. Signs of nephrotic syndrome include:

• Edema (swelling caused by fluid retention, most commonly in the legs and feet).
• High cholesterol.
• Lower-than-average levels of proteins in the blood.
• Proteinuria (foamy-looking urine caused by high levels of protein).
• Weight gain: people usually gain water weight because of the swelling.
• Fatigue (tiredness).
• Increased blood pressure, especially if the kidneys start to fail with the MN.

Some people with MN do not notice any symptoms. In these individuals, doctors may find signs of MN during a regular office visit or when testing for another issue.

How is membranous nephropathy (MN) diagnosed?

If you have any symptoms of nephrotic syndrome (protein in your urine with swelling or decreased kidney function), you should be referred to a nephrologist. A nephrologist is a doctor who specializes in diseases and conditions of the kidneys. Your nephrologist will use several tests to confirm an MN diagnosis. These tests can include:

• Blood test: Taking a sample of blood to measure levels of fat and protein.
• Glomerular filtration rate (GFR): Studying a blood sample to measure kidney function.
• Kidney biopsy: Taking a small sample of kidney tissue with a needle and having a lab examine it to see if it contains an antibody associated with MN.
• Urine test: Measuring levels of protein and blood in your urine.
• Antibody levels: blood sample to measure the levels of the antibody against the phospholipase A2 receptor.

What are the treatments for membranous nephropathy (MN)?

Treatment for MN depends on the type and cause. If you have primary MN and the levels of protein in your urine are not severe, your kidney function is stable and you have not had a complication of MN (such as a blood clot), your nephrologist may choose to use the following treatments without medications to suppress your immune system for six to 12 months since some cases may resolve on their own.

These treatments may include:

• Angiotensin-converting enzyme (ACE) inhibitors: Drugs that manage high blood pressure, lower urine protein levels and help reduce inflammation in the kidneys.
• Diuretics: Medications that remove excess fluids from the body and lower blood pressure.
• Low-salt diet: Reducing salt intake to reduce edema.
• Cholesterol-lowering medications (statins): help reduce the elevated cholesterol levels.

However, if any of the previously mentioned factors are present or the proteinuria does not decline during the observation period, your nephrologist will likely use immunosuppressive therapy.

• Immunosuppressive therapy: Drugs to stop the immune system from producing the antibody that attacks the kidneys, including:
  • Corticosteroids.
  • Rituximab.
  • Cyclosporine.
  • Cyclophosphamide.

In some people with secondary MN, treating the underlying condition may stop kidney damage from progressing.

What complications can happen if I have membranous nephropathy (MN)?

Health issues and complications from membranous nephropathy can include:

• High cholesterol (higher than average levels of fat in the blood).
• Severe swelling (called nephrotic syndrome).
• Kidney failure.

Additional complications that can happen due to MN can include:

• Deep vein thrombosis(DVT)/pulmonary embolism (PE): Blood clot in the legs or the lungs.
• Renal vein thrombosis: Blood clot in the renal vein in the kidney.

Pulmonary embolism and renal vein thrombosis can be life-threatening complications that require emergency medical treatment. Symptoms of each condition can include:

• Pulmonary embolism: Sharp chest pain that is worse when you take a breath.
• Deep vein thrombosis: Pain or swelling in one leg.
• Renal vein thrombosis: Pain on the side of your torso and/or blood in the urine.

If you experience these symptoms, call 911 or go to an emergency department.

How can you prevent membranous nephropathy (MN)?

For most cases of membranous nephropathy, there is not anything that can be done to prevent it since it is an autoimmune process. For those cases caused by other disease, treating and controlling those diseases may help reduce complications from them, such as MN.

What is the prognosis (outlook) for people with membranous nephropathy (MN)?

The prognosis for MN varies depending on the person. In some cases, the disease goes away on its own without treatment. For others the disorder can continue for many years without getting worse.

Some people with MN end up with kidney failure. These people may need a kidney transplant or dialysis (long-term treatment where a machine filters the blood for the kidneys).

MN can come back after treatment. Your nephrologist may monitor your kidney function regularly to look for signs that the disorder has returned. This monitoring will allow your doctor to treat you as soon as possible if MN recurs. Your nephrologist may also keep you on medication to suppress your immune system for longer periods of time to reduce the chances of a flare-up occurring. This practice can vary by nephrologist and the patient.

When should I see a healthcare provider about membranous nephropathy (MN)?

You will not know that you have MN based on any symptoms since many different problems can cause them. Contact your healthcare provider if you notice unexplained swelling in your face, arms or legs.

What questions should I ask my doctor?

If you have MN, you may want to ask your doctor:

• What caused my MN?
• What type of treatment is best for me?
• How long will my treatment last?
• What complications should I look out for?