Membranous Nephropathy

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What is Membranous Nephropathy?

Membranous Nephropathy (MN) is a kidney disease that can occur by itself (primary) or in conjunction with several other diseases (secondary) discussed below.  MN is one of the most common causes of the Nephrotic Syndrome (see below) in adults.  Over time this can lead to kidney failure as well.

MN is caused by the build- up of immune complexes within the kidney itself.  Immune Complexes are made when a person’s antibodies attack something they consider foreign to the body (an antigen). This is often an infection of some sort.  An antibody +an antigen = an immune complex.  These immune complexes are normally eliminated while still in the circulation. Under certain conditions they can accumulate in different parts of the body.  Both the immune complexes and the parts of the kidney where they build up  are extremely small. They  can only be seen under a microscope.  Therefore, in order to be diagnosed with MN, a person must first have a kidney biopsy.

What does it look like?

First a quick look at the kidney. Most people have two kidneys, one on each side of their lower back.  All of the blood in your body passes through your kidneys many times during the day. Each time blood goes through some of it gets filtered and cleaned by the glomeruli. This cleaning is how your body gets impurities out of the blood and removes extra water. Some of the cleaned blood becomes your urine.  Urine isn’t red like blood because the red blood cells, which give blood its color, are too big to fit through the filters.  A glomerulus (one glomeruli) is just a tiny bag of blood containers through which blood gets filtered, and all of the clean blood (urine) runs into tubes (ureters) which eventually lead to your bladder.

Below is a diagram of how the immune complexes deposit in the kidney.  Pictured is a single blood vessel from a kidney filter, shown in cross section.  Inside the circle is the center of the vessel, where blood is.  The filtering occurs through the yellow, gray, and green walls. After this it is considered urine.   The yellow is part of the blood vessel itself, and the green is part of a kidney cell called a podocyte.  The gray is a substance called the basement membrane.

Illustration of a glomerular capillary-Dr. Charles Jennette

 

The expanded box shows how the immune complexes form in detail.  The antibodies floating in the blood pass through the vessel wall and encounter the antigen.  The resulting immune complexes become stuck in that space. Over time they begin to further activate the immune system.  This activation causes inflammation and damages the kidney itself.

This damage can be seen under the microscope as a “thickening” of the vessel walls within the kidney filters.  Below are shown two filters both with a more detailed picture underneath.  On the right is a normal filter, and on the left is shown the changes of MN. This is also called Membranous Glomerulopathy.

Picture of glomerulus with Membranous-Dr. Charles Jennette

The arrows in both pictures are pointing out the thickness of the capillary (small blood vessel wall).  Notice how much thicker this wall is from a patient with MN.

Illustration of capillary with Membranous

Below is another picture of a capillary wall from someone with MN. This time it is seen by an electron microscope. This can magnify things to over a million times their normal size.

Picture of capillary wall with Membranous- Dr. Charles Jennette

The vessel wall is the large “hollow” oval extending the length of the picture.  Notice all of the slightly darker “clumps” within the capillary wall. These are the actual immune complexes, already deposited.

Illustration of Membranous stages

 

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How did I get it?

MN usually occurs in adults older than forty, and is fairly rare in children.  Men are affected more often than women. Whites are affected more commonly than blacks.  Though we know how the kidney damage occurs in MN, we don’t know exactly why the immune complexes occur in all people.  In these cases the disease is called Primary MN.  In Secondary MN, the same type of kidney injury occurs but is associated with, or maybe even caused by, another illness.  Some of the more common diseases are:

Secondary MN has also been associated with some drugs, such as penicillamine, gold, and non-steroidal anti-inflammatory drugs.  Anyone who is found to have MN, especially those over 50 years old, should be tested for Hepatitis and undergo routine age-appropriate cancer screening.

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What are the symptoms?

The most noticeable symptom of MN is often edema, or swelling, which can be serious.  This typically starts in the feet and legs. But it can move into the hips and abdomen as well.  Other symptoms include high blood pressure, high cholesterol, and a tendency to form blood clots.

Protein levels can be measured in a urine sample. Kidney function can be calculated from a blood test alone or measured more directly using a 24-hour urine collection.  MN can cause protein in the urine alone. It can also cause protein in the urine and kidney failure together. Therefore,  both must be assessed by your doctor.

None of the above symptoms or even all of them together, is specific for MCD.  If you or your doctor are concerned about MN, the only way to know for sure is to have a kidney biopsy.

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The Nephrotic Syndrome

When someone has a great deal of protein in their urine, they can often develop what is called the “Nephrotic Syndrome.”  This syndrome always includes:

It often also includes:

MN often causes the Nephrotic Syndrome.

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What is the treatment?

MN is not an easy disease to treat. Anyone with this disease should be seen regularly by a kidney specialist.   It is important to be on a medication that reduces the amount of protein in the urine.  These medications are called ACE-inhibitors (angiotensin converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers).  If urine protein levels are high, the complications of the Nephrotic Syndrome should also be considered.  Patients should receive routine cholesterol screening/treatment.  Their physicians should always remember their tendency to form clots.  Finally, patients with MN must have their kidney function monitored regularly.  If kidney function declines, certain other interventions may become necessary.

In addition to the above, many different types of immunosuppressants, or drugs that suppress the immune system, are also being used to treat MN. The most common of these are steroids.  For MN this is often combined with another type of chemotherapy, such as cyclophosphamide or chlorambucil.  Unfortunately, all of these drugs have significant side effects. Their use must be considered on a patient-by-patient basis.

Finally, if the MN is considered secondary, then it is most important to treat the underlying disease (infection, cancer, or autoimmune) or to stop the causative drug.  Often this is enough to get rid of, or at least significantly improve, the kidney disease.

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What are my chances of getting better?

Up to 40% of patients diagnosed with MN undergo a spontaneous remission within 5 years, even without therapy.  These patients do not necessarily stay in remission, however.  On average, 20 years after diagnosis, 1/3 of patients will be in complete remission, and 1/3 will have progressed to end-stage renal disease and need dialysis. Another 1/3 will be somewhere in the middle.  Those people that initially have more than a gram of protein in their urine per day for more than six months tend to do worse. Their renal function often declines regardless of therapy.

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Kidney Transplant in Membranous Nephropathy

Unfortunately, many patients diagnosed with MN will eventually progress to kidney failure.  Fortunately, kidney transplant is a treatment option for these patients.

For some general information about kidney transplant, click here.

Will the membranous nephropathy come back in my kidney transplant?

There is a 10-30% chance that the MN will return in your transplant.  Unfortunately, there are no factors that have been identified to give us an idea of patients at risk for this problem.  Generally, recurrence of the disease will occur in the first 2 years after transplant.

Is there any treatment for membranous nephropathy that comes back in a transplant?

Currently, there are no specific therapies for recurrent membranous nephropathy in the transplant.  However, some of the newer immunosuppressive drugs have been shown to be effective in treating MN in a patient’s original kidneys. They are starting to be used in transplant patients with recurrent MN.

If the membranous nephropathy does come back, will it cause me to lose my kidney transplant?

There is some controversy about the degree to which recurrent MN affects the survival of a transplanted kidney.  Some studies suggest that up to 50% of patients with recurrent MN will lose their kidney as a result of the disease.  Of all patients with MN that get a transplant, around 10-15% of them will eventually lose the kidney due to a return of the disease.

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