Dr. Bob Underwood (Host): Welcome to PedsCast, a podcast brought to you by Children's of Alabama. I'm your host, Dr. Bob Underwood. Today, we will be talking about pediatric kidney transplantation, risks involved, and Children's as a national leader in transplant. We have the privilege of speaking with an expert in pediatric kidney transplantation. With us today is the Medical Director of Pediatric Renal Transplantation, Dr. Michael Seifert. Thank you so much for joining us today.

Michael Seifert, MD: I appreciate you having me. Thank you.

Host: Absolutely. And I got a couple of questions. What are the benefits and risks of kidney transplantation as a treatment for kidney failure in children?

Michael Seifert, MD: Well, it's important that you framed it that way, Dr. Underwood. So when we speak with families about kidney transplantation, we talk about it as an option for treatment of kidney failure. We don't want it to be misconstrued as a cure or the end of the line for treatment for kidney failure because it is another way of treating it. That's to say that eventually all kidney transplants will fail and the majority of children that get a kidney transplant in childhood will need to get another transplant, if not two to three more, throughout the course of their lifetime. But we would like to make their first transplant last as long as possible because as you can imagine, it gets more difficult to do the transplant every time that you have to do it.

Host: Yeah. Just the impact of repeated surgeries, I'm imagining.

Michael Seifert, MD: That's right. Yeah, repeated surgeries and the immunosuppression regimens get more complicated to manage. And so, all those factors accumulate as you go along.

Host: So, what are the important differences between a live donor versus a cadaveric kidney transplant, in kids especially?

Michael Seifert, MD: Right. Well, there used to be bigger differences in outcomes between live donor and deceased donor transplants, meaning that we really would encourage families to do a living donor kidney if they have the option because the survival of that kidney transplant was so much longer. But now, because of improvements in surgical techniques and organ preservation, the general figures we quote is that a living donor transplant lasts about 10 to 15 years on average, whereas a deceased donor transplant lasts seven to ten years on average. So, those figures are getting closer and closer all the time.

The other thing that we mentioned is that live donor transplants are very predictable, to some extent at least, meaning that we know exactly who the donor is going to be, when it's going to happen. Those things are pre-scheduled weeks, if not months, ahead of time, whereas the deceased donor can come up very unexpectedly. Often you'll get called for potential donor kidney overnight or on a weekend or on a holiday. And the timing of that can be very unpredictable and more challenging for us to manage as well as the families.

Host: Wow. And those are definitely a big benefit to the families and the kids if they can procure live donor transplant for sure.

Michael Seifert, MD: We often will say too, that as predictable as a living donor is and that you get a plan a way ahead of time with a deceased donor transplant, once you go on the wait list, you might get called for that transplant within a matter of a few days or weeks, or could end up waiting as long as two to three years or longer. So, the unpredictability comes as that wide of a range.

Host: Yeah, absolutely. So, you mentioned long-term kidney transplant survival. In other words, how long does the kidney survive? So, what are the barriers to long-term kidney transplant survival?

Michael Seifert, MD: Well, there used to be a big barrier during the first year after transplant, meaning early on you were at relatively high risk for what's called acute rejection or the body trying to fight off the kidney as a foreign invader, similarly to how it would treat a virus or a bacteria that's not supposed to be there. But more recently, in the last 15 to 20 years, our immunosuppression regimens have become a lot more modernized and a lot more potent and a lot more effective. And because of that, we've decreased the first year rejection rates down to 10-15% or lower across the board for most patients, such that that's much less of a barrier than it used to be.

So now, we think more about long-term barriers. We're beyond the first year. We try and prevent what's called late acute rejection episodes, which are more often episodes that come up because patients aren't able to take their medicines as reliably as we'd like them to, or they have unforeseen events like infections and other things that will interfere with their ability to absorb their medications. And that leads to late acute rejection episodes that can cause a premature loss of the transplant.

Host: Wow. And 10 to 15 percent, that seems pretty low.

Michael Seifert, MD: That's right. Yeah. It used to be part of progress note in the first week in the hospital was you would say, "Awaiting first acute rejection episode." It was just part of life. And now, it's a surprise, frankly, if you get an episode of rejection in the first three to six months, you know, much less than the first year.

Host: Yeah, that's phenomenal, that really is, in advances in medicine. So, say a patient's gone through all the prep, how long can patients and families expect the transplant procedure itself to take? And how long after the procedure will they remain hospitalized?

Michael Seifert, MD: Right. So, the procedure itself there's two flavors of it that we do at our center. One is that you're just taking the donor kidney and you're sort of tucking it into the abdomen. And that's a more straightforward surgery, a smaller incision, less time involved. There's a larger version of the surgery that some kids require where it's a bigger incision in the midline through which they take out the original kidneys and then put a new kidney transplant in its place. The first more straightforward version of the surgery takes maybe two to three hours, whereas the later version of the surgery that's more involved, that could take four to five hours to go from there. Those procedures also come with different rehabilitation and followup times. The shorter, more straightforward version, we expect you to be in the hospital a week to 10 days, whereas the more involved version, let's say, you can expect to be in the hospital for two weeks or longer.

Host: Wow. And what's the most common reason that a child need a kidney transplant?

Michael Seifert, MD: In children, the most common reason would be a congenital or inherited cause of kidney disease. More often than not, there are anatomical problems with how the kidneys and bladder develop. And because of that, you're not endowed with as much kidney function as your peers without those kinds of malformations. Because of that, there's a period of time that you can grow and develop normally even without normal kidney function, but eventually that growth puts a lot of stress on the native kidney tissue that you were born with, and eventually you get to a Point where the kidneys aren't able to keep up with your metabolic demands anymore. And then, we would proceed with the transplant at that time. That could be at a school aged kind of three to four years, or preschool age rather, or could be as late as teenagers depending on how much kidney tissue and how much kidney function a particular patient was endowed with originally.

Host: Sure, absolutely. And as clinicians, we're always talking about what are other options. So, what are other treatments for kidney failure besides transplantation?

Michael Seifert, MD: I'm a little biased because I'm the medical director of the transplant program, but I always talk about our treatment being the best available compared to the other options, but there are other options available. One other way to treat kidney failure is with dialysis, either hemodialysis or peritoneal dialysis. Those are procedures that can be done in a dialysis center, some forms of those procedures can be done in the patient's home. And they're great ways of managing kidney failure and/or associated with great outcomes. But when you compare the longevity of a patient with a kidney transplant versus the longevity of a patient that remains on dialysis, the figures are pretty clear that you have better long-term outcomes with a kidney transplant. And no matter what outcome you're looking at, just pure survival, growth and development, long term cardiovascular risk, bone health, all those things are going to be better with a well-functioning kidney transplant than staying on dialysis.

Host: Yeah. And that's true no matter what age, but I'm imagining especially true for pediatric patients.

Michael Seifert, MD: That's right. Yeah, that's one reason why children have a bit of priority on the wait list for deceased donors, because it's understood by the field that a child that receives a transplant will accrue all these benefits of good kidney function. That's important to set them off on the right path for their childhood, again being growth and development, neurocognitive development, good cardiovascular health. They get all those benefits early on when it's most important to establish those patterns early. And you could argue that a fully formed adult who's already been through growth and development in childhood doesn't require those same unique benefits that a child gets from a kidney transplant. No less important for an adult to get a kidney transplant to treat kidney failure, but they don't have those same kinds of concerns that we have to think about in pediatrics.

Host: Yeah, and very time sensitive ones at that. So, what innovative approaches to kidney transplantation and care are being offered at Children's of Alabama?

Michael Seifert, MD: Well, one of biggest things that we offer is our ability to minimize the use of long-term steroids in kidney transplantation. Steroids are one of the oldest forms of immunosuppression that are available. So, we understand them the best of all the medications, but they also have the broadest set of side effects and adverse outcomes that can affect children that take them. And so, we used to think they were absolutely required in order to keep a transplant from rejecting. And we just accepted the adverse effects as part of the fact of life, kind of like early acute rejection in that first few weeks that I talked about. But now, we have some unique protocols so we can use a lot more intense immunosuppression upfront at the right time that allows us to get by with less maintenance immunosuppression over the long run, which includes mainly getting rid of steroids, and we have great outcomes with that in our program.

Host: That's phenomenal. And you're right, the big side effect profile in steroids, especially long-term use. So, here's the question really coming back to you. What are you working on to improve the quality of care provided for kidney transplant recipients?

Michael Seifert, MD: Well, one of the things we're really proud of on our program is that we were one of the founding centers of the Improving Renal Outcomes Collaborative or IROC. This is a learning health network focused on quality improvement that's based at the Cincinnati Children's Hospital and Medical Center. As I said, we were one of the first centers that got involved and were involved in developing its charter and its path to become what it is today, which is a learning health network that has, I believe, over 40 pediatric kidney transplant centers involved and was responsible for doing more than half of the pediatric kidney transplants in the country last year.

This is a network that's mainly focused on three pillars. One is improving longterm cardiovascular health and kidney transplant recipients, pediatric kidney transplant recipients rather. The second is in reducing rates of acute rejection over the longterm, because we know they have a big impact on the quality of life for patients with a transplant. And the third is exactly that, focusing on how do we make their quality of life better. You've got a kidney transplant and that comes with a lot of benefits, but how can we make sure you're getting the most out of that gift to really get the most quality out of your life and really feel like you're setting yourself aside from kidney disease as much as possible. So, we're really proud to be involved in a lot of quality improvement initiatives that were developed and come from the IROC network and have led to improvements in blood pressure control and reduced rejection rates at our center.

Host: That's phenomenal. That's phenomenal. And great goals to be shooting for too.

Michael Seifert, MD: Right. Simple work, but I think the simple stuff is sometimes the hardest to do, because we have to work to get everybody aligned and pulling in the same direction. And then once you do that, you can start to work on some of the harder things.

Host: Yeah, absolutely. So, what are some of the recent scientific discoveries that could have an impact on pediatric kidney transplantation in the near future?

Michael Seifert, MD: Well, some of the things that we're working on ourselves and with collaborators in our program is the idea of how do we detect rejection episodes in kids in a timely fashion that allow us to treat them early and prevent them from causing some of those long-term problems that we talked about earlier on. And there's a couple of ways that we're working on that in our program. One is to do what's called surveillance biopsies, which is taking a piece of that kidney transplant at a pre-specified time, whenever we think everything's going well based on all the functional testing that we have available. But surprisingly, we see that about a fourth of the time, patients that appear to be doing well from all of our labs have some early rejection hiding under the surface in their biopsy that we wouldn't have detected otherwise. We've published with our peers in that part of our program that whenever you find that rejection and treat it, it really improves their long-term outcome and their survival with the transplant. The downside of that is we're doing a lot of biopsies, which any kid that gets a transplant biopsy will tell you it's not fun.

And so, the other thing we're working on is trying to figure out what are better tests that we can do that we don't already have available that'll tell us when a kid needs a biopsy and when they don't. And so, those are both avenues of science that we're working on that are really relevant for pediatric kidney transplants in particular.

Host: Yeah, that is interesting. One of the questions I would have, is there not a good or significant biomarkers that you could just draw from the blood rather than do a biopsy?

Michael Seifert, MD: It's a great question. Like adult medicine, we've used creatinine forever as the best marker of kidney function. And it's known to be especially insensitive to detecting kidney rejection in kids until there's extensive damage already present. You think about a pediatric kidney transplant, for the most part, they're getting an adult-sized kidney and that goes into a very tiny person. And so, there has to be a lot more damage within that big kidney in order to show up in a lot of our tests as a problem with creatinine. And so, we're trying to develop tests that are more sensitive than creatinine and perform better because kids really need that. It's not a great marker in adults either, but it works better in adults than it does in kids because of the size issues that I mentioned.

Host: Yeah, absolutely. And kids don't have a lot of muscle mass, which is one of the things that generates creatinine too.

Michael Seifert, MD: That's right. That's exactly right.

Host: Yeah. Wow. In summary, anything else that you'd like to share with the listeners today? I just think pediatric kidney transplantation is a really exciting field right now. You know, I think there are some problems that are universal to adult transplant medicine that apply to pediatric medicine that we're working on, but there are also some unique issues for pediatric kidney transplants, like some of the biomarker issues we talked about that we're working on in our program. And we're really trying to make the care that we provide for kids that have kidney failure a lot better and always trying to improve. So, it's a young field and we're excited to be part of it and hopefully making it better.

Yeah, absolutely. It's very exciting. Thanks so much for joining us today and thanks for sharing your expertise.

Michael Seifert, MD: Thanks, Bob. I enjoyed speaking with you. Thanks again.

Host: For more information or to refer patients to Children's of Alabama, visit childrensal.org. That concludes this episode of Children's of Alabama PedsCast. If you found this podcast helpful, please share it on your social channels and be sure to check out the entire podcast library for other topics that might be of interest to you. Please remember to subscribe and review this podcast. Thanks for listening to this episode of PedsCast. I'm your host, Dr. Bob Underwood.