Dr. Mike (Host): Welcome to Pediatrics in Practice, a CME podcast. I'm Dr. Mike. And with me is Dr. Judith VanSickle, Medical Director of the Pediatric Kidney Transplant Program at Children's Mercy. Today, we're talking about proteinuria and hematuria in kids, and how to approach these findings in practice, when to worry, and what pediatricians really need to know. Dr. VanSickle, welcome to the show. Great to have you on again.

Judith VanSickle, MD: Thank you. Thank you again for inviting me to discuss that pretty important and I think frequently overlooked topic of blood in the urine, other way we call it hematuria, and protein in the urine, otherwise called proteinuria.

Host: Well, let's just start there. I would love to know, and I know a lot of community pediatricians would love to know how you kind of approach these. So, start with proteinuria, you know, protein in the urine. How do you approach that?

Judith VanSickle, MD: So, why do we have kidneys? We have kidneys because their job is to remove the toxins, the excess water, maintain the electrolyte and the pH, the acid-base homeostasis. How do we do that is that there is an actual fence. There is a filter inside of the kidney, okay? The job is to keep the cells, the protein, the nutrients in, and that complex filtration system is basically going to let the rest of them out. That filtration comes with like cells and then like a molecular part together, and they kind of attach like you would look like in a fence exactly.

And so, I think that's super important when we talk about proteinuria is that normally we should not have protein in the urine, okay? Except one really rare occasions, and we're going to talk about it when we talk about with teenagers. So when we have protein in the urine, then we really have to think about it, that fence opens up enough to let that protein part, the molecular part out, but not too big that actually the cellular component could come out, okay?So, having really protein in the urine is it usually related to some kind of illness that destroys that fencing barrier, typically destroys the molecular charge of that barrier.

And so, with all that saying, again, when we dip the urine and you see protein in the urine, one other thing that I want to remind a pediatrician is that you have to understand the dipstick limitations, because that's like an enzymatic process, right? Every test has a good part and bad part. Good is that you can do it in your office right away. Bad thing is that you have to understand is super sensitive. So, it picks up on everything, but it really, really not specific. So, bacteria and other stuff can also trigger it to be positive. And so, we always need to understand that if you see protein in the urine in a normal child, you should first quantify it. So, you should send it out for a further analysis.

Host: With that said about proteinuria, so your approach to hematuria, how does that differ?

Judith VanSickle, MD: Almost never, never normal to have blood in the urine. I think that's what's kind of like a key things with the compared to the two things. And really, we're going to talk about the presentation of the children, too. But with all of that saying, if you have red cells sneaking out, that means really that fenestration system is almost damaged or it's congenitally gone because you do have some other developmental problem with it. And typically, again, when you have blood coming through that filtration barrier, that is part of a systematic disease that is, again, destroying the kidney, and it's losing the blood because you cannot filtrate it, okay?

But one other thing to remember that the kidneys has no innervation. There's no innervation with it, okay? So when you see a kid who present with dark-colored urine, brown urine, you should be really much more worried than compared to the kid, and I know it's doesn't make really any sense everybody. But when you have a patient who is coming with pain for hematuria, that's never going to come from the kidney. That's really come from the lower urinary part, right, the tube, the bladder.

Host: Right. So, what findings should prompt a referral to a specialist like you then?

Judith VanSickle, MD: So if you have patients come with your clinic reporting blood in the urine, your first question should be, "Is it painful or painless?" It was confirmed that this is a painless hematuria. Please visibly look at the urine. So, take your time. And you really actually see that while it does look discolored, you do the dipstick test, then do go out and send it out because like we talk about it, the dipstick can be pretty positive for other reason too.

And then, if for sure, if you do see that there is more than five to 10 red cells under the microscope on three different occasions, or that patients also presents with other concerning symptoms, right? Swelling, rash, joint pain, high blood pressure, those patients should be definitely worked up and call us right away, because that's why we are here. That's our typical bread-and-butter nephrology, right? That's what we like to talk about a lot.

Host: Okay. I, I'm going to back up just for a sec for the community pediatrician here. And I want to talk about some initial lab tests that maybe they can run before referral to you. So, they do the urinalysis, they do the dipstick, they're going to send that off. If there's blood or protein possibly in that sample, what other tests should they be ordering right now to help you complete the picture?

Judith VanSickle, MD: And I think that's really good because, Mike, to be honest, many times we have these questions, "What other things you want me to do?" And to be honest, our main thing is give us a good explanation, give us a good history, give us a good physical exam. If you really want to do laboratory testing, that's perfectly fine just to check what's the kidney function.

So, just do a basic blood work for a basic metabolic panel, and then maybe a liver function to check on serum albumin. Again, you're looking for evidence of kidney dysfunction and evidence of losing protein, right? So, your albumin level should be low. And again, many times many pediatrician wants to do the immunological workup, the lupus workup. Don't waste your time because those tests are typically expensive, come back late. We can deal with that, and those information is really just going to be the next step. I think that's really the key thing, is dipstick confirmed with a microscopic exam and do a good physical exam and a good history.

Host: Dr. VanSickle, at that point, you're not looking for even some imaging, an ultrasound of the urinary system or that's something you're going to take care of probably down the road.

Judith VanSickle, MD: And that's another really good question because really, again, if you are talking about the true nephrology etiology of blood in the urine, right? Something that coming from the other part of the kidney, you're not really going to see a too lot of things on the ultrasound. It's fine to do one to making sure that you have two kidneys.

They're going to show that the kidneys are inflamed. If that patient comes in with a painful urination, right? So, that's when we talk about a painful hematuria, then you should do an imaging, because that's when you're looking for, right, why you have that painful hematuria is because that inner liner of the urinary collecting system got damaged, and that's where the blood's coming from. And yes, those patients you will do an imaging. And so, I think it's a really easy way to sort of sort it out in your mind. Painless hematuria, I should really work it up as a possible renal etiology. Painful hematuria, there's probably some kind of urological.

Host: Yeah. Well, Dr. VanSickle, you know, I'm a radiologist, so I want to take pictures of everything all the time. Anyways, moving on.

Judith VanSickle, MD: If I would have ultrasound in my office, I would probably—you know, again, we just don't have it, but I think it's definitely you got a good point with it. Sure.

Host: So, we're talking about, I mean, we're talking about pediatrics here, right? I mean, the age ranges are huge. When we look at protein or blood in the urine, how does your approach change from infants to adolescents to preteens? Like, can you walk us through that a little bit?

Judith VanSickle, MD: I'm so glad you brought it up, because actually that was my very first article. That's my very first publication what I did when I started as a nephrology fellow. So, having a teenager, and even a younger teenager, so like a teen who is really tall and skinny, they're going to be protein in the urine during the daytime because there's something called orthostasis. You know, you're standing, and the hydrostatic pressure, there's no really fat tissue around the kidneys. And so, because of that hydrostatic overflow, there can be some protein overfiltration, okay? So, teenager, think orthostatic first for proteinuria. And that's for a reason. You should never check or if you have a daytime, during the midday sample, you should have that standard first morning sample, which is, again, before you go to sleep, urinate, wake up, and right away that first sample, that's what you want.

Host: Right. That first void is the key one, right? Okay. Yeah.

Judith VanSickle, MD: Yep. And the key thing is to empty your bladder before you go to sleep, because, again, remember, bacteria in the bladder can produce protein, right? They can produce all sorts of bad things, right? Now, for the baby, that's a little bit difficult, right? How do I check a urine if, especially if you are just want to do a random thing? And so, a bagged specimen for that, again, cleaning the skin, putting the plastic bag on, keeping them for no longer than one hour, can give you enough sample to just do that regular, you know, testing, random testing for protein or blood in it.

And so again, remember, especially with the baby, if you do see protein but you don't have any other symptoms, otherwise the baby looks good, then the number one thing that I would first really worry about it that, well, my collection way was not clean, right? There is bacteria or something that triggering the dipstick. So, use your lab. And the lab persons are really helpful, even locally. You can send out that collected specimen for a random testing, or you call us, but you let us know that I send that specimen out, and that kind of is really helpful to interpreting that protein in that random sample. Because, of course, we're not going to do a 24-hour collection in a baby, but that will be really helping you out in that period of time. And as you're getting younger and younger, having blood and protein in the urine, again, should be even more and more concerning.

Host: But now, I mean, obviously, so 24-hour collection is not really for the infant. But when you're moving into adolescence and if you're thinking hormonal issues, maybe there's growth, stunted growth, what have you, is a 24-hour collection of hormones and stuff at that point good?

Judith VanSickle, MD: For us, 24 hours would be your standard. So for sure, we would love to have a 24-hour urine collection. Teenagers also not really like to do that. Like, who wants to walk around witha can, right? But they would do it for us if we really, really want it. So, having a random specimen for the first start, that's perfectly fine. Many of these patients, when they actually ending up for the whole workup, for example, for a stone, we will make them to do a 24-hour urine collection. But again, for a PCP office, a random specimen, again, understand when you collect it in a teenager, do it at the first morning, making sure that you send it out right away, call us, and then we will help you how to interpret it.

Host: So Dr. VanSickle, you've been doing this for a long time. You're the expert. You must know some common mistakes or misconceptions that come across your desk when evaluating these patients. Can you share some of that with us?

Judith VanSickle, MD: I think not confirming the dipstick under the microscope. That's number one thing, right? And it just can cause so much alarm for the parents, too. Like, there's a dipstick positive, there's a trace positive, but I can see nothing. The kid maybe just have bedwetting or urinary infections. Again, confirm it.

Host: How often are you seeing dipsticks not confirmed under their microscope?

Judith VanSickle, MD: Very often. Very often. Yes. Yes, very often. So, I think that's number one thing that really we're going to emphasize with it. Two, having a painless brown discolored urine is hematuria. And especially if you have a patient who has other symptoms, rash, swelling, take it seriously. I think that's other, the second thing that we see it, that because those kids are not typically symptomatic, right? Typically get later diagnosed. I think that's another thing.

And then, again, the third one, if you have a child with the painful hematuria, and they have blood in the urine, and they have protein in the urine too, Mike, that's the kid that you should have a radiology imaging, right? That's a kid that you might have UTI, you might have stones, you might have voiding dysfunction. So, imaging actually can help even to make a diagnosis for a PCP.

Host: Yeah. You know, I would assume overt blood in the urine is one thing. But you probably, you know, community pediatricians probably see more of the brown color, and they're not sure what that really means, and they should just think blood right there. Is that the point?

Judith VanSickle, MD: Yes, it's a dark tea-colored urine. I really want the pediatrician to check it. But okay, you know, especially if you have a high blood pressure, you have other symptoms, headaches, dizziness, blurred vision, just that's the kid that we probably call us. Send the urine for the exam. If you really want to do a blood work, just do that. Because those are the kids that if you're delaying the diagnosis, right, you're decreasing your chances of the treatable condition or actually think about the fence is going away, right? You want to make sure that the fence will be retaining so we can actually treat that inflammatory process on time. Don't let it to go for scar formation.

Host: So, protein in the urine, blood in the urine, we know overall it, it's not uncommon. but how is the patient normally presenting? Is asymptomatic kind of a very common way? You know, all of a sudden the doctor does a dipstick and sees some blood, but the patient has no complaints, family has no—is that the common scenario?

Judith VanSickle, MD: I think now that we're going into the the fall season and the winter season, that's going to be the most likely, right? Sore throat or respiratory infection. You saw the kid 10, 14 days later, parents call you that kind of not peeing the same. I think it's dark. Look a little bit puffy. What is going on?" Right? And that would be, again, your bread and butter typical something called post-infectious or post-streptococcal, right, you know, inflammation in the kidney.

And so, I think that is one of those symptoms that just remember—and my other favorite one is unfortunately we live in an area, right, where E. coli is really often in a summertime in the lake water. And so, there's something called aHUS, right? When you can have hemolytic process breaking down the cells, you have diarrhea. You just saw that kid. And in about five to seven days, the parents call you that, "Hey, now the urine—"

Host: Yeah. Now, the urine takes a little longer to kick in. It's post-infectious process.

Judith VanSickle, MD: Exactly. Because those poor kidneys are just there. They're just filtering and filtering and filtering, and it's just like a wastebasket, right? And so, I think that's what just you need to remember that, oh, that must be the kidney.

Host: Dr. Vansicle, again, every time you come on the show, it's fantastic. Thank you so much. The amount of information you give is incredible. But I always want to get your take on, like, what does the future look like when it comes to the laboratory test, the clinical practice of proteinuria and hematuria?

Judith VanSickle, MD: Well, we don't have an AI to replace the exam, that's for sure, and the history taking. So, I think that's number one. When you see a patient like that, good history, good exam going to save a lot with that too. Dipstick, great, use it in the office. Understand how to interpret it, understand what's the limitation of that, and then have an established lab where you know how fast you can have that lab results back. And so, I think that's really important with that.

And then, lastly, if you have any questions, just call us. We are here. We are available 24/7. We will provide you with guidelines, how to work it up. We do really like to talk to the pediatricians ahead of our time because it saves us lots of headaches and potentially can save kidney function.

Host: Dr. VanSickle, listen, I love having you on. You're awesome.

Judith VanSickle, MD: Thank you so much for the time. This was awesome again. This is the view of a transplant nephrologist, right? Who kind of sees the things from the other end. But also, like you said, kidney problem not always walks into that pediatric door. So when it walks in, just think really clearly, and then step by step we'll help you to work up

Host: Great summary. As a reminder to our audience, claim your CME credits after listening to this episode by visiting cmkc.link/cmepodcast and clicking the Claim CME button. If you enjoyed this podcast, please share it and check out the entire podcast library of topics of interest to you. This is Pediatrics in Practice, a CME podcast. I'm Dr. Mike. Thanks for listening.