Beta-2 Microglobulin Kidney Disease
Beta-2 microglobulin (B2M) is a protein that is found on the surface of nucleated cells (contain a nucleus) and functions as part of the human immune system. This protein is routinely shed by cells into the blood and is present in most body fluids, with highest levels in the blood, generally lower levels in spinal fluid, and trace levels 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, but when the renal tubules become damaged or diseased, B2M concentrations increase due to the decreased ability to reabsorb this protein. When the glomeruli in the kidneys are damaged, they are unable to filter out B2M, so the level in the blood rises.
How is the test used?
The beta-2 microglobulin (B2M) test may be used when known physical or suspected kidney damage occurs to distinguish between glomerular and tubular disorders of the kidney. B2M levels will also increase with disorders that involve overactive cell turnover and when the immune system is activated, thus is not diagnostic for a specific disease. With renal failure, it provides additional information about someone's likely prognosis and the health of their kidneys. B2M is measured in the following situations:
- In kidney disease, both blood and urine B2M tests may be ordered along with other kidney function tests such as BUN, creatinine, and urine albumin (microalbumin) to evaluate kidney damage or disease and to distinguish between disorders that affect the glomeruli and the renal tubules.
- Used to monitor persons with end-stage renal disease (ESRD)
- Excess B2M can accumulate in joint spaces (synovitis) in long-term dialysis patients; this is called dialysis-related amyloidosis (DRA). A B2M test may be used to help evaluate a person for DRA.
- B2M tests may sometimes be ordered to monitor people who have had a kidney transplant to detect early signs of rejection.
- It may also be ordered to monitor people who are exposed to high levels of cadmium and/or other heavy metals like mercury, such as may occur with occupational exposure.
When is it ordered?
Both blood and urine B2M tests may be ordered when a person has signs and symptoms associated with kidney dysfunction and a health practitioner wants to distinguish between disorders that affect the glomeruli and the renal tubules. Some signs and symptoms may include:
- Swelling or puffiness (edema), particularly around the eyes or in the face, wrists or ankles
- Urine that is foamy, bloody, pink or brownish
- Protein in the urine
- Fatigue, weakness
A urine test may also be ordered periodically to monitor a person who has had a kidney transplant or to monitor those exposed to high concentrations of cadmium or mercury to detect early kidney dysfunction.
People who have been on dialysis for five years or more may develop dialysis-related amyloidosis (DRA), a condition resulting from the accumulation of excess B2M in the blood and eventually in the bone, joint, tendon (osteoarticular structure) and other body tissues such as heart, lung, and digestive tract. It is primarily diagnosed by tissue or bone biopsy. B2M levels are performed as part of the work-up in addition to imaging studies.
What does the test result mean?
Levels of B2M in the blood vary from low levels to four times the lower limit, and this is considered normal. B2M may be undetectable in the urine.
Increased levels of B2M in the blood and urine indicate that there is a problem but are not diagnostic of a specific disease or condition.
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 damage or disease. Also, B2M levels correlate with risk of cardiovascular disease (CVD) and with cause of death in patients with kidney disease or on dialysis.
In a person who has been on long-term dialysis, an increase in B2M is associated with dialysis-related amyloidosis.
Increases in urine B2M in a person with a kidney transplant may indicate early kidney rejection.
Increases in someone who is exposed to high levels of cadmium or mercury may indicate early kidney dysfunction.
Can the test be done in my doctor's office?
How long will it take for results?
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 neurologic situations, cerebrospinal fluid (CSF) may also be tested (see the Beta-2 Microglobulin Tumor Marker test article). The results are not generally interchangeable.
If I have an elevated 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 order specific tests for cadmium or mercury in your blood and/or urine (see the article on Heavy Metals).
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 beta-2 microglobulin levels, but the test is not typically ordered to monitor these conditions.
Drugs such as lithium, cyclosporine, cisplatin, carboplatin, gentamicin, interferon-α, and aminoglycoside antibiotics can increase B2M blood and/or urine concentrations.
Increases in blood and urine B2M can be seen with certain cancers, including multiple myeloma, leukemia, and lymphoma. When there is central nervous system involvement, increased B2M may also be found in the cerebrospinal fluid (see the Beta-2 Microglobulin Tumor Marker article). B2M may also be present in infectious and cerebrovascular disorders. In cases of HIV, an inverse correlation between B2M and CD4+ T-lymphocytes has been shown to mark disease progression.
B2M is increased in patients with peripheral artery disease (PAD).
Recent nuclear medicine procedures and radiographic contrast media can affect test results.
In people with kidney disease who are undergoing dialysis, B2M can form long protein chains that can be deposited in joints and tissues, causing stiffness and pain. This condition is called B2M dialysis-associated amyloidosis.