What is monoclonal gammopathy of renal significance (MGRS)?
Monoclonal gammopathy of renal significance (MGRS) is a group of rare conditions that are grouped together because of the similar way that the kidney looks under the microscope. It includes the following conditions:
- AH amyloidosis, AHL amyloidosis and AL amyloidosis
- C3 glomerulonephritis with monoclonal gammopathy
- Crystal-storing histiocytosis
- Fibrillary glomerulonephritis
- Immunotactoid/glomerulonephritis with organised microtubular monoclonal immunoglobulin deposits (GOMMID)
- Intracapillary monoclonal IgM without cryoglobulin
- Intraglomerular/capillary lymphoma/leukaemia
- Light chain cast nephropathy
- Light chain proximal tubulopathy, crystalline
- Light chain proximal tubulopathy, non-crystalline
- Monoclonal immunoglobulin deposition disease (MIDD) – includes light chain deposition disease (LCDD), heavy chair deposition disease (HCDD), and light and heavy chain deposition disease (LHCDD)
- Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID)
- Thrombotic microangiopathy with monoclonal gammopathy
- Type 1 cryoglobulinaemic glomerulonephritis
- Unclassified MGRS.
The grouping was only defined in 2012 so research is still in the early stages.
Combined, these conditions affect around 1 in 200,000 people in the UK. They are usually diagnosed in adults over the age of 50.
What are the signs and symptoms of MGRS?
Some people with MGRS do not have any symptoms. For those who do, common symptoms include:
- Protein in the urine (proteinuria) – this is likely to only be seen when the urine is tested by dipping a specially treated paper strip into the urine (urine dipstick), although if there is a lot of protein, the urine may look frothy.
- Swelling or puffiness (oedema) – this can develop in different parts of the body, especially around the eyes and ankles.
- Shortness of breath.
- General feeling of being unwell.
What causes MGRS?
The conditions included in the MGRS diagnosis are caused by the effects of an unusual protein called a paraprotein (monoclonal immunoglobin or M-protein). Around 1 in 30 adults over the age of 50 have this protein but it does not cause any problems for the vast majority of people.
In rare cases however, damaged versions of this protein are produced, and it can then start to affect various organs of the body, including the kidneys.
Amyloidosis is caused by a build-up of a protein called amyloid in the body’s tissues. Over time, these protein deposits can damage the structure of the organs and affect their function.
Light chain cast nephropathy is a caused by a cancer of the bone marrow called myeloma.
How is MGRS diagnosed?
The initial diagnosis for most people is monoclonal gammopathy of unknown significance (MGUS) after a blood test shows high levels of a bone marrow protein called gamma globulin.
If protein is also found in the urine and/or kidney function is affected, a kidney biopsy and/or a bone marrow aspiration (in which a sample of the soft tissue inside the bones is taken) may be performed to confirm the precise MGRS diagnosis.
MGRS is diagnosed if the biopsy shows non-cancerous lesions that have been caused by the monoclonal immunoglobulin paraprotein.
Does MGRS affect other parts of the body?
Some of the conditions included in the MGRS diagnosis can affect other parts of the body as well as the kidneys.
In amyloidosis, protein deposits can cause pain and swelling in the arms and legs, loss of appetite, tiredness and easy bruising. Deposits can also build up in and around the heart, causing heart rhythm abnormalities.
Light chain cast nephropathy can cause pain in the bones and frequent infections.
Does MGRS run in families?
There is some recent research that MGRS may run in families, but the precise details of any inheritance patterns are still being investigated.
How is MGRS treated?
Some people with MGRS will not need any treatment. If their kidney function is stable and only a small amount of protein is leaking into the urine, they may just be monitored by their doctor.
If kidney function gets worse and/or more protein starts to be lost in the urine, chemotherapy may be prescribed to suppress the abnormal bone marrow cells.
A transplant may be recommended if kidney failure occurs, but MGRS can reoccur in the transplanted kidney.
Where can I get more information or support about MGRS?
For more information on light chain cast nephropathy, including its diagnosis, symptoms and treatment, visit the Myeloma UK website.
Publication date: 11/2023
Review date: 11/2026
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