Can Bence Jones protein appear in a 24 hour urinalyisis (UPEP) while the serum free light chain ratio and levels remain normal?
I read one medical abstract online that suggested that this can happen, though other studies suggest that free light chain (FLC) test can replace UPEP entirely.
I only ask because I had a serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and FLC done (all of which were negative), but did not do the UPEP. Is this something I should do to complete the testing for multiple myeloma?
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Re: Can Bence Jones appear in urine with normal FLC ratio?
Hi Sara:
It is really unlikely that you would see Bence Jones proteins in urine in someone that has normal serum FLCs. The two tests are both testing for free light chains, and its not typical that they would be getting into your urine if your serum free light chain levels are normal.
However ... the FLC test has not replaced the 24 hour urine test, which is called UPEP (urine protein electrophoresis). You are right that there are some studies that have shown discrepancies (false positives and negatives) between FLC and UPEP. Most myeloma doctors, in accordance with the treatment guidelines and disease monitoring criteria, like those established by the IMWG (International Myeloma Working Group), still have myeloma patients do both tests.
It sounds, though, like you are not a myeloma patient, but are in the process of maybe having myeloma excluded as a diagnosis? If all other tests are negative, it doesn't seem likely that a UPEP is going to show anything, so maybe your doctor is ready to move on to other tests?
What led you to be screened for myeloma to begin with?
It is really unlikely that you would see Bence Jones proteins in urine in someone that has normal serum FLCs. The two tests are both testing for free light chains, and its not typical that they would be getting into your urine if your serum free light chain levels are normal.
However ... the FLC test has not replaced the 24 hour urine test, which is called UPEP (urine protein electrophoresis). You are right that there are some studies that have shown discrepancies (false positives and negatives) between FLC and UPEP. Most myeloma doctors, in accordance with the treatment guidelines and disease monitoring criteria, like those established by the IMWG (International Myeloma Working Group), still have myeloma patients do both tests.
It sounds, though, like you are not a myeloma patient, but are in the process of maybe having myeloma excluded as a diagnosis? If all other tests are negative, it doesn't seem likely that a UPEP is going to show anything, so maybe your doctor is ready to move on to other tests?
What led you to be screened for myeloma to begin with?
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Tough Mom - Who do you know with myeloma?: myself
- When were you/they diagnosed?: January 2013
- Age at diagnosis: 45
Re: Can Bence Jones appear in urine with normal FLC ratio?
Hi Tough Mom, thanks for clearing that up, I appreciate it.
I initially went to a rheumatologist because of about one year of intermittent and increasingly chronic dull bone-type pain, in my ribs, upper spine, shoulder blades, hip bone and shin bone.
I knew that bone pain can be related to vitamin D deficiencies and that I had just recovered from a minor deficiency myself, but a doctor on a health forum said that my levels were not low enough to explain bone pain. The other thing I knew about was bone malignancies, and specifically myeloma. I have a life-long history of chronic hepatitis C virus and know that some studies suggest an increased risk of developing lymphoma and myeloma with chronic hepatitis C, so yes, I wanted to rule it out, and hence the tests. I didn't have a UPEP and nor did I have any imaging as part of the workup, but at least the SPEP, IFE and FLC were all normal.
My original post is here where I posted the results:
"Wondering if I have MGUS or smoldering myeloma" (started Apr 29, 2014)
I still don't have a diagnosis for these pains, and I also have skin burning and tingling, and now a boney lump on my thoracic spine (maybe my spine is bulging there?), so I've been referred to an orthopedist. Too many issues to count.
Anyway, thank you for taking the time to reply. I wish all of you the best of luck and good health. The last stressful month of waiting for results really opened my eyes to what a fraction of this journey must be like for others...
I initially went to a rheumatologist because of about one year of intermittent and increasingly chronic dull bone-type pain, in my ribs, upper spine, shoulder blades, hip bone and shin bone.
I knew that bone pain can be related to vitamin D deficiencies and that I had just recovered from a minor deficiency myself, but a doctor on a health forum said that my levels were not low enough to explain bone pain. The other thing I knew about was bone malignancies, and specifically myeloma. I have a life-long history of chronic hepatitis C virus and know that some studies suggest an increased risk of developing lymphoma and myeloma with chronic hepatitis C, so yes, I wanted to rule it out, and hence the tests. I didn't have a UPEP and nor did I have any imaging as part of the workup, but at least the SPEP, IFE and FLC were all normal.
My original post is here where I posted the results:
"Wondering if I have MGUS or smoldering myeloma" (started Apr 29, 2014)
I still don't have a diagnosis for these pains, and I also have skin burning and tingling, and now a boney lump on my thoracic spine (maybe my spine is bulging there?), so I've been referred to an orthopedist. Too many issues to count.
Anyway, thank you for taking the time to reply. I wish all of you the best of luck and good health. The last stressful month of waiting for results really opened my eyes to what a fraction of this journey must be like for others...
-
Sara
Re: Can Bence Jones appear in urine with normal FLC ratio?
I have Bence Jones protein present in my most recent UPEP (October 2015) and yet a normal free light chain ratio. My kappa is near the upper end of normal and lambda at a level that my free light chain ratio is just shy of being abnormally high. Also, UPEP notes below normal albumin % and above normal globulin %.
I guess it's rare, but possible, to have Bence Jones proteinuria present via UPEP though free light chain (FLC) ratio is not high.
FYI other values:
IgG kappa M spike as of October 2015 @ 0.900 g/dL , immunoparesis low IgM for over one year, smoldering multiple myeloma bone marrow biopsy 2014 10% clonal plasma cells of which 91% of all plasma cells were aberrant.
Besides most recent UPEP indicating Bence Jones protein, urine immunofixation indicated Bence Jones protein kappa proteinuria in 2014, though UPEP was negative at that time for Bence Jones protein.
I guess it's rare, but possible, to have Bence Jones proteinuria present via UPEP though free light chain (FLC) ratio is not high.
FYI other values:
IgG kappa M spike as of October 2015 @ 0.900 g/dL , immunoparesis low IgM for over one year, smoldering multiple myeloma bone marrow biopsy 2014 10% clonal plasma cells of which 91% of all plasma cells were aberrant.
Besides most recent UPEP indicating Bence Jones protein, urine immunofixation indicated Bence Jones protein kappa proteinuria in 2014, though UPEP was negative at that time for Bence Jones protein.
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pinball - Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2010 MGUS, 2014 Smoldering
- Age at diagnosis: 39
Re: Can Bence Jones appear in urine with normal FLC ratio?
Pinball's explanation makes a lot of sense to me.
In this situation, it's not the serum free light chain ratio you should be looking at, but rather the individual free light chain (FLC) values. Note that you can have a normal FLC ratio even though one (or both) of the free light chain levels could be approaching the upper limit, or be above the above the upper limit(s), of what is considered to be normal. In that case, the excess lambda or kappa serum free light chains could spill over into one's urine and show up as Bence Jones proteins in your urine - even though you have a normal serum FLC ratio.
In this situation, it's not the serum free light chain ratio you should be looking at, but rather the individual free light chain (FLC) values. Note that you can have a normal FLC ratio even though one (or both) of the free light chain levels could be approaching the upper limit, or be above the above the upper limit(s), of what is considered to be normal. In that case, the excess lambda or kappa serum free light chains could spill over into one's urine and show up as Bence Jones proteins in your urine - even though you have a normal serum FLC ratio.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Can Bence Jones appear in urine with normal FLC ratio?
FYI since my post over 1 year ago:
Re: the presence of Bence-Jones protein:
My free light chain (FLC) ratio was normal until the fall of 2016, when it reached approx 1.9, and as of this month it is 2.21 (basically it was approx 0.9 in the summer of 2013 with an IgG kappa M-spike of approximately 3.75 g/dL and, as my M-spike climbed, so did the FLC ratio.
My M-spike as of the past year or so has finally topped out at 0.900 for more than 1 year, while my FLC ratio continues to climb to 2.21 as of this month. The M-spike is remaining the same, yet my kappa FLC level is rising from around 19 - 25 the past year, and the lambda levels decreasing a bit at the same time the kappa has risen, making for the 2.2 abnormally high FLC ratio (with 1.65 being the top of the normal FLC ratio range).
In my case, it seems that with the M-spike remaining about the same in the past 18 months as the FLC ratio climbed from near 1.65 to now at 2.2 over 18 months more so due to the lambda levels dropping than the kappa levels rising (though they did rise from around 19 to 25).
Not sure on the significance of a constant M-spike but yet rising FLC ratio (due mostly to the uninvolved lambda level dropping more than kappa rising).
Back to Bence Jones appearing in my urine protein electrophoresis (UPEP) studies over the past 18 months:
Until the past year, Bence Jones protein was proven to be found via urine immunofixation even the past few years in my case while my UPEP results began to indicate a slight monoclonal peak in the gamma region (this was when my FLC ratio just increased above the normal range).
As of last fall, once my FLC ratio neared and has now surpassed the 2.0 mark (making it above normal), there's a measurable amount of Bence Jones protein found in my UPEP results of 17 mg per day.
The increased FLC ratio has matched the measurable appearance of BJP in my UPEP results (all the while again my M-spike is near the same).
It stands to reason that an increased FLC ratio as well as increased kappa FLC value is resulting in more free light chain proteins (BJP) leaking thru my kidneys, therefore resulting in a measurable amount of Bence Jones protein found in my UPEP results.
Many folks have higher free light chain values than mine (which are abnormal but not crazy high by any means) yet no Bence Jones proteinuria, so I would think it's more of a renal function element that is resulting in measurable Bence Jones protein in my case though my M-spike (blood) has not risen and my free light chain levels, while abnormally high, are not very high.
Many folks I've seen post labs with a much higher FLC ratio and M-spike (blood) yet no Bence Jones proteins detected via UPEP.
I'm hoping that the now "regular" for me Bence Jones protein levels are not going to result in any form of kidney damage over time. In fact, I've not even thought about progressing from my current (barely) smoldering multiple myeloma to active multiple myeloma, but more so I'm concerned about possible kidney tubule damage tied to the increased Bence Jones protein (as my kidneys are no longer absorbing all proteins but allowing a bit to "escape" or "leak" thru the kidney into urine to be found via UPEP results.
I've had 3 bone marrow biopsies in the past 12 months (1 in April 2016 a year ago, and 2 late last fall <also 2016> ), and the values of each were near the same - similar to my 2014 April bone marrow biopsy results, by the way. Note my bone marrow biopsy last fall was bilateral testing, therefore I'm counting it as 2 results.
I'm glad that my care team always performs a 24-hour urine test (UPEP) as the Bence Jones protein finding was key as it could indicate the change of light change deposition or other renal related issues that may result in an issue well before I'd ever progress to active multiple myeloma.
Anyway, hope someone found this interesting.
Re: the presence of Bence-Jones protein:
My free light chain (FLC) ratio was normal until the fall of 2016, when it reached approx 1.9, and as of this month it is 2.21 (basically it was approx 0.9 in the summer of 2013 with an IgG kappa M-spike of approximately 3.75 g/dL and, as my M-spike climbed, so did the FLC ratio.
My M-spike as of the past year or so has finally topped out at 0.900 for more than 1 year, while my FLC ratio continues to climb to 2.21 as of this month. The M-spike is remaining the same, yet my kappa FLC level is rising from around 19 - 25 the past year, and the lambda levels decreasing a bit at the same time the kappa has risen, making for the 2.2 abnormally high FLC ratio (with 1.65 being the top of the normal FLC ratio range).
In my case, it seems that with the M-spike remaining about the same in the past 18 months as the FLC ratio climbed from near 1.65 to now at 2.2 over 18 months more so due to the lambda levels dropping than the kappa levels rising (though they did rise from around 19 to 25).
Not sure on the significance of a constant M-spike but yet rising FLC ratio (due mostly to the uninvolved lambda level dropping more than kappa rising).
Back to Bence Jones appearing in my urine protein electrophoresis (UPEP) studies over the past 18 months:
Until the past year, Bence Jones protein was proven to be found via urine immunofixation even the past few years in my case while my UPEP results began to indicate a slight monoclonal peak in the gamma region (this was when my FLC ratio just increased above the normal range).
As of last fall, once my FLC ratio neared and has now surpassed the 2.0 mark (making it above normal), there's a measurable amount of Bence Jones protein found in my UPEP results of 17 mg per day.
The increased FLC ratio has matched the measurable appearance of BJP in my UPEP results (all the while again my M-spike is near the same).
It stands to reason that an increased FLC ratio as well as increased kappa FLC value is resulting in more free light chain proteins (BJP) leaking thru my kidneys, therefore resulting in a measurable amount of Bence Jones protein found in my UPEP results.
Many folks have higher free light chain values than mine (which are abnormal but not crazy high by any means) yet no Bence Jones proteinuria, so I would think it's more of a renal function element that is resulting in measurable Bence Jones protein in my case though my M-spike (blood) has not risen and my free light chain levels, while abnormally high, are not very high.
Many folks I've seen post labs with a much higher FLC ratio and M-spike (blood) yet no Bence Jones proteins detected via UPEP.
I'm hoping that the now "regular" for me Bence Jones protein levels are not going to result in any form of kidney damage over time. In fact, I've not even thought about progressing from my current (barely) smoldering multiple myeloma to active multiple myeloma, but more so I'm concerned about possible kidney tubule damage tied to the increased Bence Jones protein (as my kidneys are no longer absorbing all proteins but allowing a bit to "escape" or "leak" thru the kidney into urine to be found via UPEP results.
I've had 3 bone marrow biopsies in the past 12 months (1 in April 2016 a year ago, and 2 late last fall <also 2016> ), and the values of each were near the same - similar to my 2014 April bone marrow biopsy results, by the way. Note my bone marrow biopsy last fall was bilateral testing, therefore I'm counting it as 2 results.
I'm glad that my care team always performs a 24-hour urine test (UPEP) as the Bence Jones protein finding was key as it could indicate the change of light change deposition or other renal related issues that may result in an issue well before I'd ever progress to active multiple myeloma.
Anyway, hope someone found this interesting.

-
pinball - Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2010 MGUS, 2014 Smoldering
- Age at diagnosis: 39
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