I was thinking about free light chains (FLCs) the other day and got to wondering about the tests for FLCs and their half lives.
An FLC has a half life of about 6 hours. It seems to me that between the FLCs aging in one's blood serum (before being picked up by one's kidneys) and the combination of the FLCs aging in a urine specimen jar, that you would end up with extremely few FLCs in a 24 hour urine sample.
Do 24 hour UPEPs actually measure the FLCs themselves, or do they instead measure the components that the FLCs degrade into? Or do the FLCs cease to degrade when they are outside one's body so that a lab has more to measure?
Forums
7 posts
• Page 1 of 1
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: 24 hour UPEP and free light chain (FLC) half life
Hi Multibilly, I would assume that refrigerating the blood and urine before testing at certain temperatures halts the degradation of the light chains in the fluid.
-
terryl1 - Name: Terry
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August 10, 2011
- Age at diagnosis: 49
Re: 24 hour UPEP and free light chain (FLC) half life
This is a good question, Multibilly. A couple of quick questions that may help us get to a solution.
First, do we know that the half life of free light chains is a result of degradation, as you suggest? When it comes to the half life of drugs in a patient's body, for example, the half life is not always (or at all?) due to degradation. It's due to the time it takes the body to remove the drug from the patient's system.
Is it possible that something similar goes on with free light chains? That is, is it possible that the half life is not due to the FLCs degrading, but due to the amount of time it takes for them typically to be removed from the body?
Second, half life is exactly what it sounds like -- the time it takes on average for something to decrease in amount or concentration to half its peak level, assuming no further production of that "something."
What that usually means, however, is that two half lives after the peak, the amount / concentration is one quarter of the peak. Three half lives out, and the amount / concentration is one eighth. Etc.
It's not necessarily the case that, a little bit after the half life has gone by, nothing is left of whatever is being measured.
So, if UPEP samples are tested at a set time after collection, the normal ranges may take into account any "degradation" that is still ongoing.
If any degradation is actually still ongoing (see my first point).
First, do we know that the half life of free light chains is a result of degradation, as you suggest? When it comes to the half life of drugs in a patient's body, for example, the half life is not always (or at all?) due to degradation. It's due to the time it takes the body to remove the drug from the patient's system.
Is it possible that something similar goes on with free light chains? That is, is it possible that the half life is not due to the FLCs degrading, but due to the amount of time it takes for them typically to be removed from the body?
Second, half life is exactly what it sounds like -- the time it takes on average for something to decrease in amount or concentration to half its peak level, assuming no further production of that "something."
What that usually means, however, is that two half lives after the peak, the amount / concentration is one quarter of the peak. Three half lives out, and the amount / concentration is one eighth. Etc.
It's not necessarily the case that, a little bit after the half life has gone by, nothing is left of whatever is being measured.
So, if UPEP samples are tested at a set time after collection, the normal ranges may take into account any "degradation" that is still ongoing.
If any degradation is actually still ongoing (see my first point).
Re: 24 hour UPEP and free light chain (FLC) half life
I had a good conversation with my onc today on the value (or lack thereof) of 24 hour UPEPs. He personally doesn't use them anymore. His reasoning is the following:
1. You already get good data from the serum FLC and serum kidney function tests.
2. He's never seen a situation where a 24 hr UPEP indicated something that wasn't already represented by the the serum tests. That is, the 24 hr UPEP never showed anything that contradicted the serum test results, at least in his experience.
3. He's incredulous of many of the 24 hr test results because many patients simply don't follow all the exact procedures required to get a good sample. You simply don't have that issue with serum tests.
So, maybe one's doc might have a good reason to order a 24 hour UPEP, but I might encourage you to at least get their reasoning on why they think it's required. I, for one, am perfectly happy not to have to deal with it
1. You already get good data from the serum FLC and serum kidney function tests.
2. He's never seen a situation where a 24 hr UPEP indicated something that wasn't already represented by the the serum tests. That is, the 24 hr UPEP never showed anything that contradicted the serum test results, at least in his experience.
3. He's incredulous of many of the 24 hr test results because many patients simply don't follow all the exact procedures required to get a good sample. You simply don't have that issue with serum tests.
So, maybe one's doc might have a good reason to order a 24 hour UPEP, but I might encourage you to at least get their reasoning on why they think it's required. I, for one, am perfectly happy not to have to deal with it
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: 24 hour UPEP and free light chain (FLC) half life
Dear Multibilly,
Great question about free light chains and UPEP.
A couple of points
1. The UPEP is an important part of IMWG response criteria and, for those with measurable disease, it is critical to do UPEP to appropriately determine response.
2. The serum FLC can vary and fluctuate widely based on, for example, renal function and infection.
3. The UPEP is very helpful because with it we can see other important complications like proteinuria (not due to Bence Jones proteinuria) and due to hypertension/diabetes, and importantly in myeloma patients: amyloid, and renal toxicity due to bisphosphonates. Amyloid can present at time of diagnosis or later in myeloma disease, and progressive proteinuria on UPEP is often a first sign that we may be dealing with amyloid.
We and the IMWG continue to recommend UPEP as part of standard studies to evaluate response and disease status.
UPEP does not need to be refrigerated and the key is to collect for a 24-hour period consistently.
All the best.
Great question about free light chains and UPEP.
A couple of points
1. The UPEP is an important part of IMWG response criteria and, for those with measurable disease, it is critical to do UPEP to appropriately determine response.
2. The serum FLC can vary and fluctuate widely based on, for example, renal function and infection.
3. The UPEP is very helpful because with it we can see other important complications like proteinuria (not due to Bence Jones proteinuria) and due to hypertension/diabetes, and importantly in myeloma patients: amyloid, and renal toxicity due to bisphosphonates. Amyloid can present at time of diagnosis or later in myeloma disease, and progressive proteinuria on UPEP is often a first sign that we may be dealing with amyloid.
We and the IMWG continue to recommend UPEP as part of standard studies to evaluate response and disease status.
UPEP does not need to be refrigerated and the key is to collect for a 24-hour period consistently.
All the best.
-
Dr. Jatin Shah - Name: Jatin Shah, M.D.
Beacon Medical Advisor
Re: 24 hour UPEP and free light chain (FLC) half life
Thanks Dr. Shah for clarifying the utility of UPEP. Your response was very helpful as I have too have read/heard it may no longer be a necessary diagnostic due to the sensitivity of the serum FLC assay.
My multiple myeloma specialist continues to use it along with the serum FLC assay and he explained these precise reasons, i.e., Progressive proteinuria which would could be Albuminuria (rather than Bence Jones/FLC's) if Amyloidosis.
He also explained to me that BJ in the urine likely occurs if kidney dysfunction is present or if the serum FLC threshold causes it to spill into the urine as the kidneys can't quite keep up with breaking down/processing the free light chains from the blood. Is my understanding accurate?
I always appreciate reading your thorough responses to the forum questions.
All the best,
Dana H.
My multiple myeloma specialist continues to use it along with the serum FLC assay and he explained these precise reasons, i.e., Progressive proteinuria which would could be Albuminuria (rather than Bence Jones/FLC's) if Amyloidosis.
He also explained to me that BJ in the urine likely occurs if kidney dysfunction is present or if the serum FLC threshold causes it to spill into the urine as the kidneys can't quite keep up with breaking down/processing the free light chains from the blood. Is my understanding accurate?
I always appreciate reading your thorough responses to the forum questions.
All the best,
Dana H.
-
DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: 24 hour UPEP and free light chain (FLC) half life
Thanks for the follow up Dr. Shah! This is good information to know.
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
7 posts
• Page 1 of 1