Monoclonal Gammopathy of Renal Significance (MGRS)

What is monoclonal gammopathy of renal significance (MGRS)?

Monoclonal gammopathy of renal significance (MGRS) is a group of conditions that cause kidney damage. The damage is caused by certain plasma cells, or B cells (types of white blood cells), making too many copies of themselves (clones). These plasma cells make faulty antibodies called M proteins that can build up in your organs and damage them.

MGRS isn’t cancer. But a small number of people with MGRS will go on to develop cancers like multiple myeloma.

Types of MGRS

Over a dozen conditions are considered types of monoclonal gammopathies of renal significance. They can be categorized by what part of your kidney the M proteins affect. These include glomerular diseases, tubulointerstitial diseases and intra-renal vascular lesions.

Glomerular diseases

Most types of MGRS are glomerular diseases (glomerulopathies). These conditions damage the small blood vessels in your kidneys. They include:

• Renal amyloidosis. This includes AL amyloidosis, AH amyloidosis and AHL amyloidosis.
• Cryoglobulinemic glomerulonephritis (CG).
• Fibrillary glomerulopathy (FGN).
• Immunotactoid glomerulopathy (ITG).
• Glomerular diseases associated with monoclonal protein. This includes light chain and heavy chain deposition diseases.

Tubulointerstitial diseases

Tubulointerstitial diseases affect the tubes that bring filtered nutrients and fluids back to your blood (tubules), and the tissues around them. They include:

• Light chain Fanconi syndrome (LCFS).
• Light chain proximal tubulopathy (LCPT) without crystals.
• Crystal-storing histiocytosis.

Intra-renal vascular lesions

Intra-renal vascular conditions affect the blood vessels of the kidneys. Atypical hemolytic uremic syndrome (aHUS) is a type of MGRS where clots block your kidneys’ smallest blood vessels.

How common is MGRS?

MGRS is very rare. It’s estimated that less than 1% of people have it. It’s more common in people over age 60.

What are the symptoms of monoclonal gammopathy of renal significance (MGRS)?

Symptoms of MGRS depend on what type you have. You might experience:

• Tiredness (fatigue).
• Swelling in your lower legs, ankles or feet. Swelling sometimes also affects your belly (abdomen), arms or face.
• Nephrotic syndrome.
• Foamy or frothy pee (urine). This can be a sign of proteinuria.
• Needing to pee frequently (frequent urination).
• Blood in your pee (hematuria) or pink-tinged pee.
• Nausea and vomiting.
• POEMS syndrome.
• Numbness, tingling or weakness (signs of neuropathy).
• Discolored (light or dark) patches of skin.
• Shortness of breath (dyspnea).

What causes monoclonal gammopathy of renal significance (MGRS)?

Damage to your kidneys caused by M proteins leads to MGRS. M proteins are malformed antibodies — proteins that fight infection — that don’t work properly. Damaged copies, or clones, of certain white blood cells (plasma cells or B cells) make M proteins.

Some people have plasma cell clones that make M proteins without causing any organ damage (monoclonal gammopathy of undetermined significance, or MGUS). In people with MGRS, the proteins build up in your kidneys, damaging them.

What is the most common cause of monoclonal gammopathy of renal significance?

Experts aren’t sure what specific causes lead to MGRS. Autoimmune disorders, genetic changes, infections and environment could all contribute.

What are the complications of MGRS?

The plasma clones and the kidney damage caused by MGRS can lead to serious complications, including:

• Chronic kidney disease (CKD).
• End-stage renal (kidney) disease.
• Kidney failure.
• Progression to other diseases. In some people, the plasma cell clones multiply so much that it leads to multiple myeloma (MM), a cancer of your white blood cells. MGRS can also develop into other cancers, like Waldenström macroglobulinemia, chronic lymphocytic leukemia (CLL) or B-cell lymphoma.

How is MGRS diagnosed?

A provider diagnoses MGRS with a kidney biopsy. They’ll take a sample of tissue from your kidney and test it for M proteins. They might also test samples of your blood, pee (urine) or bone marrow.

Can MGRS be treated?

Providers use treatments similar to cancer chemotherapy to treat MGRS. These medications kill problematic cells or stop them from making more copies of themselves. Other medications help reduce inflammation. The goal of treatment is to keep your kidneys working and stop damage to them.

Providers also sometimes treat certain cases of MGRS with a stem cell transplant that replaces your damaged cells with healthy ones. If you have severe kidney damage, you may need dialysis or a kidney transplant.

Specific medications and procedures used to treat MGRS

The medication your provider treats you with depends on what kind of MGRS you have. Some treatments include:

• Monoclonal antibodies (rituximab, daratumumab).
• Proteasome inhibitors (bortezomib, carfilzomib and ixazomib).
• Immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide).
• Alkylating agents (cyclophosphamide, bendamustine, melphalan).
• Corticosteroids (prednisone, dexamethasone).
• Autologous stem cell transplant.

Side effects of treatment

Chemotherapy can cause many unpleasant side effects and even organ damage. Providers select treatment carefully to give you the most benefits and reduce the risks of severe side effects. Some side effects you may experience include:

• Anemia.
• Bleeding.
• Constipation.
• Diarrhea.
• Fatigue.
• Increased risk of viral, bacterial and fungal infections.
• Loss of appetite.
• Nausea and vomiting.

Can MGRS be prevented?

Since we don’t know what causes MGRS, there’s no specific way to prevent it.

What can I expect if I have MGRS?

MGRS is treatable but usually doesn’t completely go away. It often comes back after treatment. If you have severe kidney damage, you might need a kidney transplant.

About 18% of people with MGRS go on to develop multiple myeloma. Your provider will monitor you with blood and urine samples to catch any progression as early as possible.

How long can you live with monoclonal gammopathy of renal significance?

How long you can live with MGRS depends on what type you have and how severe it is. People with less kidney damage have a better prognosis (outlook) than people with severe kidney damage. For instance, in one study, people with amyloidosis related to MGRS lived an average of 10 years after diagnosis. But those without amyloidosis lived longer. Similarly, people who respond well to treatment have the best outcomes.

How do I take care of myself?

Follow any recommendations your provider gives you for taking care of your kidney health at home. This might include limiting things like alcohol and managing other risk factors for kidney disease, such as hypertension and diabetes. While this can’t directly treat MGRS, it might help reduce your risk of further kidney damage. Your provider can also help you manage any side effects of treatment.

When should I see my healthcare provider?

See a provider if you have symptoms of kidney issues, including swelling, frothy or pink-tinged pee, or needing to urinate frequently or hardly at all.

What questions should I ask my doctor?

It might be helpful to ask your healthcare provider:

• What treatments are available?
• How can I prevent kidney damage?
• What new or worsening symptoms should I look out for?

A note from Cleveland Clinic

MGRS is a serious condition that can cause life-threatening kidney damage. Most people with MGRS don’t develop cancers. Your provider will monitor you to catch and treat any new issues as soon as possible. New treatments can improve your quality of life and reduce your risk of severe illness.