BETA - What is a urine protein electropheresis (UPEP) and when should it be done? Why is a 24 hour urine sample necessary?

What is a urine protein electrophoresis, UPEP, test? And why is a 24-hour urine sample so important, especially at diagnosis? In this Health Tree University lesson, we break down what UPEP measures and why a full 24-hour urine collection gives doctors critical information when diagnosing conditions like multiple myeloma and other plasma cell disorders. What is a urine protein electrophoresis, UPEP? UPEP stands for urine protein electrophoresis. Whenever somebody has a plasma cell disorder, whether it be MGUS or myeloma or amyloid, the cancer cells are making an abnormal protein that's being released into the blood. And this protein tends to float in the blood and we can pick up this protein by an S-PET and an immunofixation. But all of this protein gets processed by the kidneys. And whenever the kidney is damaged or the kidney has reached maximum capacity of processing this protein, it's going to be dumping it in the urine. So we can identify and pick up this protein in the urine at times. Before we had free light chains as a test that we could use regularly for blood, we had to rely on UPEP because we had cases of patients who did not have any detectable S-PEP or abnormal protein in the blood, but we were finding it in the urine because that's where it was being concentrated. So that is something that we're still doing for several reasons. One, we want to make sure that when somebody's being diagnosed that we have turned all stones and made sure that we looked everywhere. So if we find it in the blood, we also want to make sure if it's detectable in the urine or not as a baseline. We don't need to use it on a regular basis while we're treating patients, but then it's also very important to use it whenever we're confirming remission. If we suspect that somebody's in remission and we don't detect that protein in the blood, we want to make sure that we do a UPEP to see if we still detect that protein in the urine or if it's been cleared by the urine as well. And that way we can be guaranteed that the patient has met the criteria for a remission and what depth of remission they've achieved. But to be honest, UPEP is a test that is now facing out little by little and free lichens are taking over that test. We still are going to be using it a lot of the times and one of the reasons why we do it is more for study purposes. A lot of the clinical trials that have been done on multiple myeloma relied heavily on UPEPs back in the days and if we want to be comparing data from now to data from back in the days, we want to be using similar variables and UPEP is one of those tests that we want to be using as a constant during those studies. The UPEP is normally done on a 24-hour urine collection. Some physicians refer to the UPEP as the 24-hour urine test. The UPEP is the test and the 24-hour urine collection is the method used to obtain the sample for that test. The 24-hour urine collection has been an essential component in the tiny amounts of protein in the urine. It's usually less than 150 milligrams per 24 hours so there's not a lot of protein that comes down into our urine. In the case of multiple myeloma, what you might find is predominantly lichens. Now those lichens when they come down in the urine historically have been called Benz Jones and Benz Jones is synonymous with lichens. So it was called Benz Jones proteinuria meaning a protein in the urine. Now that's mostly what you see. If you read the reports carefully more often they will say perhaps a small IgG kappa and that's because a tiny amount of the large one can filter plus kappa and it's mostly the lichen that filters down into the urine. So you want to do that for measuring. Before we had the free lichen this would be a way in which someone could detect what was called back then the Benz Jones escape meaning if you had a patient that went from producing IgG kappa to kappa only you might suddenly see that the IgG was dropping in the blood but the patient appeared to be progressing with myeloma and if you were not to do the urine you wouldn't know that because they didn't have the free lichen because the protein was coming down into the urine. So that's what was called the Benz Jones escape. Well nowadays most of that honestly can be detected through the blood so in my particular practice I only do collection of urine for difficult circumstances or at the beginning. It is exactly 24 hours which is so difficult for our patients because of course it means that you sort of have to collect both during daytime and nighttime. So you start, mark your start time and you sort of collect every time that you go to the bathroom, every time you go to void until 24 hours later. So why this is important is because oftentimes a fluctuation in the results is really because the amount of time isn't accurate. So say if our patients forget flush toilet in the night and we count that as 24 hours it's really not 24 hours. Not an easy test for sure. It requires the patient to collect the urine for 24 hours. So you can essentially see how that may you know make that person really immobile at home, you know just at home. So the logistics of being able to collect the 24 hour urine are difficult for the patient to maintain actually and while I see the value of getting that done at diagnosis or certain milestones during a patient's journey I don't think it needs to be done all the time. When we look for abnormal protein in the urine the reason that we collect the 24 hours has more to do with the concentration of the urine at different time in the day is actually quite variable. So to understand just how much really average that the cancer protein spill into the urine and normalize for this varying concentration you actually get those 24 hour number and it tends to be a bit more accurate comparing to if you were doing spot check. Now there's also a situation where if the amount of abnormal protein in the urine is small you could miss it if you're doing a random urine that also is where the 24 hour kind of come in. It will also tell us not only how much of the cancer protein is in there but also how about good normal protein that should not spill out into the urine if there were a lot of the normal protein that spill into the urine because the kidney filtration system is off they'll also reflect extra concerns because it reflects extent of kidney damage. There's also an entity where the actual abnormal protein hurt the kidneys in different ways and it caused loss of good protein such as amyloid doses so it's you're also going to see that when we send that urine protein electrophoresis oftentimes we look at both. Is there the wrong kind of thing there? How about the good kind of thing? Is it leaving the body inappropriately? Why is a 24-hour urine sample necessary at diagnosis? Now there's another important that one must look at when you first do the urine collection and that is looking for an excessive amount of albumin in the urine and the reason for that is when when we doctors see a lot of albumin and if it reaches a certain level we call that nephrotic syndrome so it's a protein spilling disorder of the kidney and that would be a big red flag for someone to say maybe this patient has amyloid doses and this would have very profound implications on how we think about a person who has a newly found monoclonal protein. If I have a patient who say has a small IgG it has some free light chain abnormalities but they don't have anemia or the calcium is normal normally we would say we're going to observe that it could be an m-gus but if that same person has a lot of amount of this protein in the urine I would investigate further for amyloid doses and if amyloid doses were to be documented that person needs immediate treatment because you want to prevent the complications for amyloid doses so that's why it's so important to pay attention to that you know right at the beginning of an evaluation. A 24-hour urine sample allows us to get information about the amount of protein that gets spilled into the urine so depending on the type of protein that gets spilled we may assess if a patient is at a risk of amyloid doses versus light chain casnopropathy or nothing at all. It is something that I routinely get at diagnosis but it is a very cumbersome test so you know 24-hour urine at diagnosis I feel is critical in us being able to assess a patient's risk of developing the kidney issues that I alluded to earlier such as myeloma casnopropathy or amyloid doses. It still is a standard quantitative way to measure the tumor burden at baseline but also it's good to also be able to use that to hopefully rule out other kinds of damages to the kidneys amyloid doses for example. You will also see that if a patient is going on clinical trial they need to have a particular amount that will qualify them so you'll see that sometimes your doctor will try to get to that 200 milligram because that is still part of the guideline for measurable disease. I think for our patients who might have been followed for monoclonal gummopathy for undetermined significant rem gas or smoldering myeloma if there is a concern that they may be progressing that will be the time to also do urine protein lithophoresis just to get a sense as a number sometimes in the light chain in the blood or in protein started to edge up are you starting to see changes in the urine because that will tell us about whether the kidneys are at risk because once you start to see a cancer protein in the urine even if it doesn't hit the criteria for symptomatic myeloma it's giving a doctor like me a warning sign that no now we need to be on close watch we're not doing this once a year we're bringing our patients in a little bit more frequently to be sure that we're not missing out on an opportunity to treat them as early as possible when there's enough indication to treat. How often should 24-hour urine samples be repeated? What are the changing international myeloma working group guidelines on the need for 24-hour urine sample? I don't think it's necessary all the time and I think that's the question we need to answer. Does it really like in the response assessment I believe it's IMWG response assessment you have to have a certain threshold above which you cannot have you know the light chains in the in the urine. I think that's what Dr Banerjee showed with the SWOG analysis a clinical trial analysis that he showed was that it doesn't really change the end the disease criteria for the patient so we are having our patients get tests that impose a lot of burden on them and it may not be necessary. So the protein that we see in the urine typically when it's myeloma protein it tends to be of a light chain subtype because these are small molecules which just filter right into the urine we now have a newer test that allow us to measure light chain in the blood and that tend to be more sensitive comparing to the 24-hour urine meaning that if patients were to progress oftentimes it will change first before we start to see abnormal protein in the urine so we're hoping that in the future we just might be able to do less frequent 24-hour urine collection and may be able to rely a little bit more on the blood test which is so much easier to obtain you're already getting serum protein lotto for instance this is really just another test that runs alongside the turnaround time is also faster anything that needs a protein gel run and a pathologist doing a calculation that's going to take five to seven days a blood test for the light chain that's typically a 24-48 hour turnaround time so there's been recent study looking at data collected from clinical trial asking a question well these patients they all have both the serum light chain and the urine collection if we close our eyes on the urine results are we miscalculating patients response and it turned out that is affecting less than one percent of patients so hopefully the up won't be something that's necessary in the future but at a particular point i think at baseline it's important or if someone's kidney function change without an explanation they're responding to treatment their kidney function decline it's important to catch the 24-hour urine to understand what's happening and also hopefully another good time to do it would be to confirm complete remission based on the criteria that we use right now complete remission still does require not having the presence of abnormal protein in the urine the role of 24-hour urine collection in multiple myeloma is diminishing with a trend toward more convenient and equally effective monitoring methods while it remains a critical tool at diagnosis and in specific scenarios routine use is being reconsidered in favor of alternatives like serum free light chain assays and spot urine tests moreover the international myeloma working group imwg is considering updates to their guidelines to de-emphasize the need for 24-hour urine testing except in specific cases like al amyloidosis to track your testing results sign up for a health tree account once your medical records are connected you can view your test results by clicking the track my disease button on your dashboard you can also find personalized treatment options and relevant clinical trials based on your profile click the link in the description to join today