Concern about Globulin-Predominant UPEP Proteinuria Pattern

@stlmark Welcome to Mayo Clinic Connect. I have CKD stage 4 (chronic kidney disease). I also have albuminurea (protein in the urine) that my nephrologist keeps a close eye on. Having said that, I am unfamiliar with the UPEP protein composition that you refer to. (It is all Greek to me, literally!) Hopefully another member who has some experience with this will respond soon. In the mean time, do you have a good working relationship with your nephrologist and do you trust this provider?

@stlmark Let me also add my welcome to Mayo Clinic Connect!

As @cehunt Cheryl mentioned, is your nephrologist a trusted member of your medical team? What was the purpose of your 24 hour collection? And, seeing that the balance of your labs are in an acceptable range, what is your eGFR? So many times we want to take a singular result and pronounce possible conditions, but in truth it is important to look at the overall results, and trends.

For me, my 24 hour collections since 1988 showed high levels of protein. This was interpreted as a result of my systemic Lupus, and the doctors went no further, for years. In 2015 I had a kidney biopsy done due to concerning values, and was diagnosed with a very rare kidney condition. This is an example of what I was referring to above.

Is this the first time you have had this test? High globulins in a UPEP can indicate inflammation of infection, also, so if you have been sick or not feeling well, any test results can be skewed. Has your nephrologist talked to you about repeating the test?
Ginger

Thank you, Cheryl. I really appreciate your encouragement.

My nephrologist is confident that the protein composition in my urine isn’t concerning, but she did say it’s reasonable to get a second opinion if I’m still worried—which I am. My primary care provider is referring me to hematology, since the excess globulins in my urine could suggest overproduction of certain proteins. My SPEP came back normal, so I’m hoping hematology will still agree to evaluate me further.

I’ll update once I know more—thanks again for listening!

Hi Ginger, thank you so much for the warm welcome and for sharing your experience. It’s incredibly helpful to hear how others have navigated complex diagnostic paths.

This was my first 24-hour urine protein electrophoresis and it revealed a globulin predominant profile, specifically elevated alpha and beta globulins, with no monoclonal spike. My nephrologist wasn't concerned and felt no further workup was needed but encouraged me to seek a second opinion if I remained uneasy. My GI doctor, who is also board certified in internal medicine, ordered a follow-up 24-hour urine protein test. It again showed mild elevation, slightly higher than what was seen on the electrophoresis.

Given this, my primary care physician is now referring me to hematology. The thinking is that this pattern could point to abnormal globulin production. I’m hopeful hematology will evaluate further even though my SPEP was within normal limits.

My concern is that globulins are typically too large to be freely filtered and are usually reabsorbed in the tubules, so their presence in significant amounts could reflect either a tubular dysfunction or an overproduction issue. I’ve also developed persistent foamy urine this year, which has been consistent and is unlike anything I’ve experienced before. On top of that, I have multiple kidney cysts that haven’t yet been fully characterized.

My eGFR has remained stable, and other labs like creatinine, CBC, and CMP have generally looked fine. I haven’t had any recent infections that I know of, though I’ve had COVID at least twice, most recently in January. I’ve also been experiencing a range of systemic symptoms including night sweats, cold extremities, and appetite loss, and overall I just haven’t felt well since summer 2023.

I’m very interested in repeating the 24-hour collection and pursuing more targeted testing such as markers of tubular injury to get closer to understanding what’s going on.

Thanks again for your support and guidance. It really means a lot.

Mark

@stlmark I hope you will let us know what the repeated testing shows? Staying on top of things can certainly be a challenge!
Ginger

I was diagnosed with CKD stage 3a in January- GFR 48, a drop from 72 a year earlier (looking back on labs). "It's normal to have a decrease as you get older" is the story that PCPs have been telling their patients. My Nephrologist also told me not to worry about the protein in my urine or my high iron. Although my father died when I was in college, I knew he had phlebotomies (my younger siblings didn't know)... today I know it as Hemochromatosis. My recent gene tests showed I had 2 of the genes for the disease. So, with that, my suggestion is that you take a look at your eGFR and if its 60 to 89, then that is Stage 2...according to the American Kidney Fund, etc. Make sure for yourself that your GFR stays "normal". My Best. K.