Beta-2 Microglobulin Kidney Disease
The test is rarely requested when investigating kidney disease due to poor specificity. However it may be requested when you have symptoms and signs associated with kidney dysfunction; due to possible cadmium kidney toxicity. However the main use of B2M in the UK is in multiple myeloma (see the Beta-2 Microglobulin Tumour Marker article) not in kidney disease.
Beta-2 microglobulin (B2M) is a protein that is found on the surface of cells and functions as part of the human immune system (component of MHC class I). This protein is routinely shed by cells into the blood and is present in most body fluids, with the highest levels found in blood and very low (trace) levels found in urine.
In the kidneys, B2M passes through blood-filtering units called the glomeruli and is then reabsorbed by the renal proximal tubules, structures that reclaim water, proteins, vitamins, minerals, and other vital substances. Normally, only small amounts of B2M are present in the urine. If the renal tubules become damaged or diseased, B2M concentrations increase in the urine due to the inability of the tubules to reabsorb this protein. If the glomeruli in the kidneys are damaged, then they are unable to filter out B2M, so the level in the blood rises.
How is the sample collected for testing?
The test can be done on blood or urine. A blood sample is obtained by inserting a needle into a vein in the arm. Urine can be collected as a random sample or a 24-hour urine sample. Please follow any instructions you are given by your healthcare professional.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed
How is it used?
The beta-2 microglobulin (B2M) test may be used in rare circumstances when kidney damage has occurred to distinguish between the two most commonly affected sites, glomeruli and tubules. It does not replace front-line kidney function tests such as urea (also known as BUN), creatinine, and microalbumin. B2M is also non-specific in that it will increase with disorders that involve overactive cell turnover and when the immune system is activated, thus cannot diagnose a specific disease. Outside routine clinical practice, e.g. for research purposes, it might be used to monitor end-stage renal disease (ESRD), provide information on prognosis and to detect kidney transplant rejection.
B2M, as levels are higher in kidney disease, is implicated in dialysis-related amyloidosis (DRA) as the protein can accumulate in joint spaces (synovitis) in long-term dialysis patients. A B2M test may be used to help evaluate a person for DRA. Measurement of B2M is also reported to be useful in detecting heavy metal poisoning (as the heavy metals can be toxic to kidney tubules), such as in occupational cadmium or mercury exposure. It is neither sensitive (only rises late on in the condition) nor specific enough for widespread and routine use in this area and should only be interpreted with/after heavy metal analysis.
When is it requested?
This test is not used commonly for investigation of kidney disease however both blood and urine B2M tests may be requested when a person has signs and symptoms associated with kidney dysfunction and a healthcare professional wants to distinguish between disorders that affect the glomeruli and the renal tubules. Some signs and symptoms of kidney dysfunction include:
- Swelling or puffiness (oedema), particularly around the eyes or in the face, wrists or ankles
- Urine that is foamy, bloody, pink or brownish
- Protein present on a urine dipstick test
- Fatigue, weakness
Very rarely B2M may be tested in a person who has had a kidney transplant or has been exposed to high concentrations of cadmium or mercury. Dialysis-related amyloidosis is primarily diagnosed by tissue or bone biopsy, therefore B2M levels are only rarely performed in addition.
What does the test result mean?
Normal levels of B2M in the blood vary, but at low levels. B2M is normally even lower in concentration, or undetectable, in the urine.
Increased levels of B2M in the blood and urine may indicate a kidney problem but are not diagnostic of a specific disease or condition for example also being raised in some blood cell cancers.
In someone with signs of kidney disease, increased levels of B2M in the blood and low levels in the urine indicate that the disorder is associated with glomeruli dysfunction. If B2M is low in the blood and high in the urine, then it is likely that the person has renal tubule dysfunction.
In a person who has been on long-term dialysis, an increase in B2M has been associated with dialysis-related amyloidosis.
Increases in urine B2M in a person with a kidney transplant may indicate kidney rejection.
Increases in someone who is exposed to high levels of cadmium or mercury may indicate kidney toxicity.
Is there anything else I should know?
Conditions associated with an increased rate of cell production or destruction, severe infections, viral infections such as CMV (cytomegalovirus), and some conditions that activate the immune system, such as inflammatory conditions and autoimmune disorders, can cause increases in B2M levels, but the test is not typically requested to monitor these conditions.
Drugs such as lithium, ciclosporin, cisplatin, carboplatin, interferon-α, and aminoglycoside antibiotics e.g. gentamicin can increase B2M blood and/or urine concentrations by causing kidney damage primarily.
Increases in blood and urine B2M can be seen with certain cancers, including multiple myeloma, leukaemia, and lymphoma. When there is central nervous system involvement, increased B2M may also be found in the cerebrospinal fluid (see the Beta-2 Microglobulin Tumour Marker article). B2M may also be present in infectious and cerebrovascular (stroke) disorders. In HIV B2M can indicate disease progression but is no better than the current markers used so has not replaced the standard tests.
Recent nuclear medicine procedures and radiographic contrast media can affect test results.
Should everyone have a B2M test?
Can the test be done in my doctor's surgery?
Can I choose either a blood or a urine B2M test?
In most cases, the sample tested will be dictated by the reason that the test is being performed. It may be necessary to do a blood test, a urine test, or both together. In certain neurological situations, cerebrospinal fluid (CSF) may also be tested (see the Beta-2 Microglobulin Tumour Marker test article). The results are not generally interchangeable.
If I have an elevated urinary B2M, does it mean that I have been exposed to cadmium or mercury?
Generally, no. It means that you may have some early kidney damage that affects your renal tubules. If you work with or suspect that you have been exposed to cadmium or mercury, then your doctor will request specific tests for cadmium or mercury in your blood and/or urine (see the article on Heavy Metals).
Elsewhere On The Web
Patient: Information Sheet on Chronic Kidney Disease
British Kidney Patient Association: Support Group and Information
Renal Association: List of Good Websites with Reviews for a Variety of Information
HSE: Working with cadmium