Hello friends 👋

In this episode of The Incubator podcast, hosts Ben Courchia and Daphna Barbeau welcome Dr. David Askenazi and Dr. Tara Beck to discuss neonatal nephrology. The conversation explores the challenges of defining and diagnosing acute kidney injury (AKI) in newborns, highlighting the variability in nephron numbers at birth and the complexities of interpreting creatinine levels in the first days of life.

The guests discuss the long-term effects of neonatal AKI, the importance of follow-up care, and strategies for supporting kidney health in the NICU and beyond. They emphasize the need for a partnership between neonatology and nephrology to improve outcomes.

Dr. Askenazi introduces the Neonatal Kidney Collaborative (NKC), explaining its mission to advance research, education, and advocacy in neonatal nephrology. Dr. Beck shares her experience as a trainee involved with the NKC, highlighting the mentorship opportunities available.

The episode concludes with a look towards the future of neonatal nephrology research, including potential therapies and the evolving approach to renal replacement therapy in newborns. This informative discussion provides valuable insights for both neonatologists and nephrologists caring for vulnerable newborns.

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Find out more about the Neonatal Kidney Collaborative here:

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Short Bio: David Askenazi MD, MSPH, FAAP, FASN was born in Mexico City and grew up in El Paso, Texas. He attended the University of Texas at Austin where he received a Bachelor of Arts in Psychology.  He received his medical degree from the University of Texas Medical Branch at Galveston. He completed pediatric residency training at the Austin Pediatric Education Program, followed by a fellowship in Pediatric Nephrology at Baylor College of Medicine / Texas Children’s Hospital. He completed a Master of Science in Clinical Research at the University of Alabama at Birmingham (UAB).

Dr. Askenazi joined the faculty in the Department of Pediatrics at UAB as an Assistant Professor in 2005 and was promoted to Full Professor in 2016.  He was appointed the inaugural W.Charles Mayer Endowed chair of Pediatric Nephrology in 2021. He founded and is currently medical director of the Pediatric and Infant Center for Acute Care Nephrology (PICAN) at Children’s of Alabama/ UAB.  As Medical Director, he oversees the acute renal replacement therapies, plasmapheresis, peritoneal dialysis and photopheresis programs.

Dr. Askenazi has received numerous research and education grants from industry, FDA, NIH, and nonprofit foundations. He has published original manuscripts on multiple topics, primarily related to understanding and improving outcomes in hospitalized neonates and children with and at-risk for kidney disease.  He has written multiple invited reviews and chapters and is regularly invited to speak at national and international meetings.He founded and currently serves as Board Chair of the Neonatal Kidney Collaborative (NKC) (www.babykidney.org). He founded and is the current Chief Scientific Officer for Zorro-Flow Inc.

Short Bio: Dr. Tara Marie Beck is a graduate of the 2019 Class of Rowan University School of Osteopathic Medicine. She is currently a post-graduate-year (PGY) 5 trainee pursuing dual fellowship training in Neonatology and Pediatric Nephrology at the University of Pittsburgh Medical Center (UPMC).  Tara was born and raised in South Jersey (go birds!) and attended the University of Delaware’s Honors Program where she majored in Neuroscience. She returned home to South Jersey to attend Rowan SOM where she was an active member on campus. Tara won the President's Award at the Rowan SOM Graduation recognizing her for academic excellence and community service.

After graduating Rowan SOM, Tara ventured back across the Delaware River to complete her Pediatric Residency training at Nemours Children’s Health. Throughout residency, she developed a passion for Neonatology and thanks her mentors, Drs. Kelley Kovatis and Deborah Tuttle, for inspiring her to pursue NICU and challenge her to complete her residency research project focusing on fluid management of extremely low gestational age neonates.

Following her residency training, Tara started her Neonatology Fellowship at UPMC where she further discovered her niche in Critical Care Nephrology, which is a particularly emerging field in pediatric medicine and a new frontier in Neonatology. Tara is one of four people internationally completing dual training in Neonatology and Pediatric Nephrology and has emersed herself in the field through her involvement in the Neonatal Kidney Collaboration’s Six-Two Crew, a Neonatal Nephrology collaboration for trainees to immerse themselves in the field under the mentorship of the pioneers of the field, including Dr. David Askenazi. Her fellowship research project focuses on fluid management during Neonatal ECMO.

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The articles covered on today’s episode of the podcast can be found here 👇

Advances in Neonatal Acute Kidney Injury.

Starr MC, Charlton JR, Guillet R, Reidy K, Tipple TE, Jetton JG, Kent AL, Abitbol CL, Ambalavanan N, Mhanna MJ, Askenazi DJ, Selewski DT, Harer MW; Neonatal Kidney Collaborative Board.Pediatrics. 2021 Nov;148(5):e2021051220. doi: 10.1542/peds.2021-051220. Epub 2021 Oct 1.PMID: 34599008 Review.

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The transcript of today's episode can be found below 👇

Ben Courchia MD (00:01.46)

Yes, I think that some of the points that you guys have brought up are quite interesting. I think that I was reading a paper that you co -authored, David, with Michelle Starr, where you mentioned that the variability, for example, in the number of nephrons that a baby can be born with really ranges from something like a couple hundred thousand nephrons to two to three million nephrons. And I think that range alone is such a...

such a staggering number. I mean, this is kind of, it's not a small range and that can I think help us understand what you guys are describing in terms of the variability in the outcomes. I guess as we talk about the neonatal kidney and we're going to talk about long -term outcomes, I think when one of the topics of discussion that's been very prevalent is kidney injury. And I'm curious what your thoughts are on why has it taken us so long to...

sort of come up with a definition of kidney injury. When especially when we look at the rates of kidney injury that are reported in the literature, I mean, obviously now using these newer definitions, but this is something that's present in about like up to 40 % of the kids that we see that are just born preterm, that's excluding the babies with HIE and content heart disease. So why hasn't taken us so long to sort of clearly say, all right, this is what kidney injury looks like.

David Askenazi (01:23.196)

Yeah, one of the reasons is that creatinine is a very difficult measure in anyone to interpret. We learned that it's a balance between the muscle breakdown and kidney removal, but it's not a perfect marker of kidney injury. It's a marker of kidney function. And so if you, for example, are dehydrated,

then your creatinine will go up because you're going to be removing less creatinine. But that's very different than if you develop enough for toxic injury. So you could potentially have an injury to your tubules but not have a change in function. And alternatively, you can have a change in function without damaged tubules. And so that's one of the concepts I think that is difficult to grasp. And some of the new biomarkers that are coming, I think are going to help us understand

the different phenotypes of AKI that we're seeing in the NICU. The other part that is also challenging is that the creatinine rate of decline over the first week or two of life differs by gestational age. And so when you're thinking about creating a definition using a measure that's supposed to be dropping over the first five, six days of life, it's hard to talk about what happens

with a change in function where you're looking for a rise. So the example that I'll tell you, if you have a term baby whose creatinine is one and a week later their creatinine is still one, that baby has kidney injury because it didn't do what the kidney is supposed to do. The kidney, the creatinine didn't drop like it was supposed to. So that makes it a little bit confusing. I think, you know, once, you know, once you establish a steady state,

creatinine level, which is probably somewhere around day three or four of life, depending on what your maternal creatinine was, depending on how much kidney tissue the baby has, then it's really not that difficult. You're looking for a change in function. You're looking for a change in creatinine. But what's, I think, made it difficult for everybody and made everybody kind of put their hands up and say, well, we don't know what to do here, is how to deal with that change in creatinine.

David Askenazi (03:48.444)

first week of life. What we've learned to do in a lot of our studies is basically just ignore the first two days and say, well, the first two days the baby is just trying to find its new steady state. And then after that, you look for changes in creatinine from that point forward. It makes it difficult to know if the baby has kidney injury on the first 48 hours of life. But if you're looking at population data or looking at research studies, that's

Ben Courchia MD (03:59.348)

Mm -mm.

David Askenazi (04:16.924)

become the simplest thing to do.

Ben Courchia MD (04:19.892)

And it's difficult because those early creatinine measurements are not always the most reliable when we're talking about preterm infants. And that could be a source of confusion as well. So I mean, I think that's always something of concern.

David Askenazi (04:34.396)

Yeah. And then the other thing that I'll show you is that in the awaken study, for example, when we looked at the prevalence of AKI across different institutions, the prevalence rate was anywhere between 2 % and 57%. And the main reason is that some people didn't check creatinine. So if you never check a creatinine in your NICU, guess what? You'll never have AKI. If you never check a brain ultrasound, you'll never have IVH in your hospital.

Daphna Barbeau (04:55.683)

Hmm. Makes sense.

Daphna Barbeau (05:02.083)

Mm -hmm.

David Askenazi (05:02.716)

And so what I think a lot of programs are starting to do is starting to really think about how to protocolize not only in the first week of life, but then beyond that, how to protocolize that timing of creatinine. We should be measuring creatinine when patients are at risk for problems with kidney failure, if they're septic, if they're going to have surgery. We should be watching the creatinine carefully. But if you're never checking it, then you know.

You're never going to find it.

Daphna Barbeau (05:36.035)

That makes total sense. And I think I found some of the articles on the website, which we'll talk about near the end of the show, and some of the work that you are doing individually and as a collective group. I think there are some kind of things that we universally understand are risk factors for kidney injury, like medication use, hypotension, but there are lots of risk factors, both

prenatal, which I think we don't think about very often, and of course postnatal, insults to the kidney that can lead to acute kidney injury. Can you guys talk about some of the kind of less commonly, we're less commonly aware of risk factors for AKI?

David Askenazi (06:26.908)

The way I think about it is during the perinatal time point, it's got to do with any maternal conditions and really how the baby comes out. After the first week or so, then you're back to kind of the standard risk factors that affect anybody who's got critical illness. The ones you mentioned are for toxic medications, ischemic conditions, major surgeries.

times where you're going to have intravascular depletion and sepsis in of itself can cause acute kidney injury regardless of whether the kidneys being perfused. So there's changes that happen in the microcirculation of the kidney that can cause kidney injury in septic patients even if they have good renal blood flow. So those are things that are common to any human and any animal.

I think what you're bringing up is what's unique about babies, and it's really that perinatal area. So what we've learned is certainly things like APGAR scores, maternal medications, maternal, interestingly preeclampsia seems to be a protective factor against AKI in the first week. We've scratched our heads a lot, and we've seen it in multiple studies. But we think it's protective probably because it

it's a signal that the baby's okay. And it was, you know, it was the baby was delivered early because the mom was having preeclampsia. So the baby comes out healthy, if you know what I mean. But those are some of the things that I think are unique to the neonatal population.

Daphna Barbeau (08:10.115)

I think also some of the things, I mean, the definition certainly has been in flux, but some of the things I think clinically we worry about, we wonder about at the bedside is, okay, now I'm seeing these changes on my lab findings. I may or may not be seeing some changes in urinary output. What are some ways that we can really support?

babies really focus on the kidney during these times where we see that there's definitely injury happening to better support neonates. Maybe, Terry, you want to take a stab at this one?

Tara (08:48.718)

Yeah, happy to. So some of the things that I know I do and advocate for whenever I'm on service, especially that first 48 hours where the baby's still finding their steady state. So creatinine may not be quite as helpful if there's any concern historically or with a questionable creatinine. I'd really dose all medications or what I'll do is I'll make sure I'm getting early bank troughs or bank troughs sooner than we otherwise would and dose a baby's vancomycin. For instance, if that's a medication they're going to be on based on bank trough.

Gentamicin, I'll opt to use cephapine as opposed to gentamicin, making sure I'm really dosing cephapine. Making sure blood pressure is good. A lot of times the baby or baby kidneys like a little bit higher blood pressure. So it could be as easy as just making sure that their blood pressure, their MAPs are a little higher than we maybe otherwise would just to make sure we're, you know, allowing for good adequate kidney perfusion and making sure that the basics, things like that.

are really looking good in order to protect the baby or instead of waiting for that creatinine to double the next day with labs and then taking action. I think it's all about early identification and early action.

Daphna Barbeau (10:02.499)

Thank you. That makes a lot of sense. I like this concept about protection and doing what we can. I'd like to ask about, you know, are there any things we can do then as treatment therapy for a kidney injury once we see it? But I did have a question based on what you mentioned. And obviously, as we're seeing younger, earlier, smaller babies, we're certainly, I think,

more acutely aware of how the early medications that are kind of the mainstay of what we do in the NICU are affecting the kidney. And there's still no change, I think, in our primary antibiotic recommendations for the smallest babies. We always start with AMP and GENT, but I wonder if you anticipate that will change over time and maybe for under a certain threshold we'd be, we would start.

empirically with cefepime instead of something like gentamicin in the highest risk population.

Tara (11:06.158)

I think it's a curious thing and I'm wondering if it's something that I'm going to be able to see during my lifetime career of something, especially babies, maybe those born very early or extremely preterm babies, those with maternal risk factors, maybe mom was having blood pressure instability around the time of delivery. It's a great question, Daphna, and I think that it's something I'll be curious to see.

Daphna Barbeau (11:30.403)

And then David, any things we can do for babies once we see that injury has occurred? Okay, we know about fluid restriction to work on fluid overload, and I think that's where our main area of focus is. But are there other things we can be doing to support babies once we recognize that there's injury and we're starting to see some changes, say, in urine and abs?

Daphna Barbeau (11:59.459)

Hope when you're muted.

David Askenazi (12:04.156)

Yeah, I think that the question is how do we optimize the medical management of a baby who's not making enough urine to maintain its needs, right? And so it starts by asking, well, what's the reason and why is the baby holding on to fluid in the first place? Tara's point, I think is a great one, that we tend to think about keeping maps at the correct gestational age level.

But that may not be enough in someone who's got a little bit of abdominal tension, a little bit of heart dysfunction. And so really kind of pushing that blood pressure up slowly to see if you can find a better threshold where the kidneys will be happier. Other things that we do in our program, we think about albumin a lot and it's very controversial. But we give concentrated albumin to our patients who have low albumins.

to assure that the fluid is maintained in the intramuscular volume. The use of diuretics certainly is important. The message I think that the nephrology community has learned in other populations is really that if diuretics are working, then that's great, but trying a new diuretic or a new regimen of diuretics every day without making

progress is probably not a great strategy. And so there's this idea that you give diuretics, you look for a response, and then you learn from that response after a couple of hours to decide what to do next. If it's working, keep going. If it's not working, then you've got to put your hat back on and keep thinking. And then after you go through all that, one of the exciting places that neonatal nephrology is going

is that there's now extra corporal therapies that have been designed with lower volumes so that we can dialyze babies. And so once maximal medical management has occurred, getting an access place so that you can support the baby and support the prevent further fluid overload, provide all the nutrition that you need is really starting to

David Askenazi (14:27.804)

be adopted across the United States and across Europe and other countries across the world. So that part's really exciting as well.

Ben Courchia MD (14:37.353)

Tara, any thoughts on that?

Tara (14:42.158)

Yeah, I think just like David said, and really, I think the most exciting thing going on in neonatal nephrology is those extracorporeal therapies. I know a lot of places are using more so things like the Aquadex machine, Carpe Diem, even using the CRRT machines, the Prismax, especially in patients with ECMO. So I think that there's a lot around the corner coming in terms of who's going to be available and how we're going to offer these therapies to these kids.

And I would say that getting nephrology involved sooner rather than later is always the best thing. I think there's this notion sometimes that once the baby is a kilo or so fluid overloaded with a rising creatinine, that there's something magical that nephrology is going to be able to do. And I certainly wish that there was, but I think just getting them involved early in terms of coming up with strategies to concentrate fluids and use of diuretics and then potentially then the use of these extra.

sooner rather than later.

Ben Courchia MD (15:42.057)

Very interesting. And I think that speaks to something that I've read being mentioned where there's like this crosstalk between the kidneys and other organs and that you can't really just say, the kidney will recover and then everything else will fall into place. But there's really an impediment to try to really address this sooner rather than later to actually prevent further multi -organ dysfunction. Can you, can you tell us a little bit about that?

David Askenazi (16:07.644)

Yes, so if you take an animal and you cause ischemic kidney injury, okay, without fluid overload, just by causing the kidney to get ischemic, there's an upregulation of cytokines and inflammatory mediators. And if you go into the lung, you could see that there's now permeability of the capillary membrane.

there's fluid overload in the lungs, again, without a change in fluid status, as one example. And so, AKI is not just an isolated condition that causes the BUN creatinine to go up. It's an inflammatory systemic problem that affects the entire body. And people have written a lot about Cardio -Renal Syndrome and the AKI lung access. There's data

that talks about AKI and immune systems. There's data that talks about AKI and gut. And then, again, that's all data before you even start to talk about some of the consequences of AKI, like fluid overload and the impact that fluid overload has on pulmonary edema, on gut mobility, on heart function, et cetera, et cetera. So this idea that the kidney is an isolated organ is...

is really not true. It's a multi -systemic problem that occurs when a person or an animal develops acute kidney injury.

Ben Courchia MD (17:35.017)

Hmm.

Ben Courchia MD (17:44.105)

Tara, I wanted to ask you a question and maybe start it off with you because I think as a fellow, we were discussing this with colleagues that maybe 20, 30, 40 years ago, really, there was a lot of emphasis being placed on delivering bad news and patients passing. But thankfully today we have patients surviving and the bulk of our training really has moved away from delivering the unfortunate news of a patient passing, but more so towards what are the long -term outcomes of the patients that we care for?

and what are some of the ramification of their comorbidities or so on and so forth. I'm curious with your dual background and your expertise, how do you approach the counseling of families when it comes to babies who do have some form of kidney injury, especially as we learn more and more in recent months and years about their long term outcome?

Tara (18:33.486)

Yeah, absolutely. So I think that it's something, especially with the dual training, that it's just made my skills in this area stronger. Because of course, like you said, with the NICU, our outcomes are still a little unknown, but survivability is getting better and better. So with that comes a little bit of uncertainty when we're sending families home about what's that going to look like? What are they going to look like in school 10 years from now? What are they going to be able to do from a physical therapy standpoint, occupational therapy standpoint?

Ben Courchia MD (18:41.033)

Mm -hmm.

Tara (19:03.374)

The kidneys the same way and it's very much a watch and wait sort of thing So I think that in terms of you know talking to families about kidney injury and especially sending families home Knowing that their child may sooner rather than later end up on dialysis It's something that it is. It's a conversation that I've gotten stronger at having especially with this full background and I think that it is it's just a lot of watching and waiting and

Thankfully, I've had the chance with a couple of families already to be able to establish a rapport with their family, with their baby in the NICU, but then also take care of them as a provider in the nephrology world, which I think is such an asset then to be able to have and to be able to build this rapport with these families and be able to take care of them. So it is, it's unfortunately a lot of watching and waiting.

Ben Courchia MD (19:42.249)

Mm -hmm.

Ben Courchia MD (19:53.609)

I see. And David, I wanted to ask you this question because I think the mirage of kidney injury in the NICU is that the kidney injury sort of gets better, right? You may have a form of AKI early on and things normalize apparently, but there still is an underlying risk of long -term consequences. And so I think the nephrology follow -up is something that has been dismissed for a long time.

because we said, the baby had some kidney injury at day three of life and now it's day 155 and we're doing much better. How do we change the paradigm? What is your recommendation in terms of which, because we, I mean, I guess our goal is also to be mindful of healthcare utilization. So how do we navigate which patients really is at the highest risk, which one needs closer follow -up, which ones can go without follow -up? I mean, what is your approach to these patients that we see in the NICU that

eventually have to go home.

David Askenazi (20:50.684)

Yeah, Ben, that's an excellent question that people have been debating for a long time. And thankfully, we came together, led by Michelle Starr, who got an R13 grant from NIH, to ask that question exactly. And so approximately 50 people from multiple disciplines came together in February to really pose that question and help provide some consensus guidelines.

And those will be published hopefully in the next coming months. But essentially what the guidelines are saying for term kids who have asphyxia, for example, for kids, cardiopulmonary bypass kids, as well as the preemies, one of the first things that the guidelines are going to say is that before they go home from the NICU, there should be a really good kidney health assessment done. Because if you find someone that has

hypertension, someone who's got, you already can document chronic kidney disease, well that's easy. Those kids need to be seen right away by someone who's got expertise in nephrology and hypertension. But that's not going to be, that's going to be a small part of the group. The other group is, we will end up recommending to keep them in kind of risk categories. And depending if they're super high risk or kind of moderate risk,

Ben Courchia MD (22:10.569)

Mm -hmm.

David Askenazi (22:15.004)

have a periodic assessment. All these kids should be having blood pressures checked routinely, the extremely premature neonates. There's pretty good data that shows that that's not happening. And then depending on just the gestational engine, other risk factors, having an assessment, a full kidney health assessment around two years of age, we think is reasonable. Again, if they had normal creatinine around the time of discharge.

Ben Courchia MD (22:27.753)

Mm -hmm.

Ben Courchia MD (22:44.489)

Right. Right. And in terms of counseling, because I think Tara mentioned this, I mean, NICU parents are fed up with us by the end of the hospitalization. I feel like how important is it for them to be given a thorough outlook as to what can potentially happen from a kidney standpoint? Because we know

David Askenazi (22:44.7)

And they've had.

Ben Courchia MD (23:10.409)

that these infants, as we discussed, because they may not have as many nephrons and because they have all these comorbidities, are really at risk of needing dialysis, of having end -stage renal disease and all these complications. But when do you decide that, hey, I'm going to talk to them about potentially dialysis in the future, as it is probably the happiest day of their lives and they're getting close to going home, in which patients do you broach the subject with and which do you say, you know what, we'll see how the baby does at two years and we'll talk about it then.

David Askenazi (23:39.58)

Yeah, I think it has to be a partnership because I'm probably not going to see them, especially if the neonatologist screens them and everything looks okay. So I think it has to be a partnership and I think it's providing them education that is useful. So scaring them to say, hey, by the way, down the road, your child may be on dialysis when they're 20. I don't think it's really helpful. I think what is helpful is to help them understand that there's things that are available

Ben Courchia MD (23:44.457)

Mm -hmm.

David Askenazi (24:09.756)

try to prevent them from developing worsening kidney disease, making sure they're not hypertensive, avoiding motion and Advil as much as possible in those early years, coming to attention if they're having fever to make sure they're having a urine check. So those practical things, I think, need to be in the forefront of education because we know that a little bit of hypertension

Ben Courchia MD (24:13.161)

Mmm.

David Askenazi (24:39.74)

can make that patient develop chronic kidney disease as age two as opposed to maybe an age 15 or 30.

Daphna Barbeau (24:47.619)

Interesting. That's really helpful. And certainly some pearls that I have not used in my discharge teaching. So I'm going to store those away. Since we're talking about anticipatory guidance and you kind of alluded to this, Ben's question was there is this group, the biggest group of babies is that, you know, we saw a little, some changes, creatinine definitely changed, the urine output changed, and that they've recovered.

What are the most common long -term effects that we're seeing in that population where, again, sometimes that brief kidney injury has been forgotten by the time of discharge, but what are we seeing in the adolescent age into adulthood?

Daphna Barbeau (25:39.267)

Maybe David, if you want to take this one.

Tara (25:40.718)

I was going to say I'll let David take one.

David Askenazi (25:41.148)

Yeah, sure, sure. So it's a great question and it's a little bit difficult to answer because it depends issue, right? So you can have a 24 week baby who's born with kind of less nephrons than his counterpart 24 weekers and as Ben alluded to, there's a large variability who will not have any AKI during their hospitalization.

but they'll have kidney function of 50 % at two years of age. In an ancillary project that we did with the PINA trial, we found that 25 % of babies less than 25 weeks gestation, between 24 and 25 weeks, had a GFR less than 90 at two years of age. And so part of it is, how much kidney tissue does a baby have to start with?

Alternatively, we've had kids that are born term who had a very severe placental abruption, for example, who never recovered their kidneys and have severe AKI that makes them dialysis dependent and end up needing transplants. So it's really kind of, it depends. It depends how much kidney tissue the baby starts with and then how many and how severe the AKI episodes occur.

Daphna Barbeau (27:05.219)

And I think that's really an interesting point that even in the babies where maybe we didn't identify AKI, but they were born extremely preterm, there still are some long -term effects and risk factors to long -term health. Is that right? Yeah. Can you tell us a little bit about what that monitoring looks like on the outpatient side?

David Askenazi (27:21.468)

Absolutely.

Daphna Barbeau (27:30.147)

is it mostly labs? Is it really following the blood pressure really closely? I know that's the one that certainly even in the baby who, you know, we didn't flag in the NICU that, that long -term hypertension is, is, is an ongoing risk factor.

Tara (27:49.326)

Yeah, I'm happy to talk a little bit about that and what it looks like in terms of labs, like you said, Daphna. So obviously getting a creatinine, a lot of times we'll get something called a cystatin C, at least where I'm at UPMC, just to follow again, it's thought to be maybe a little bit more sensitive to the kidney, to monitoring the kidney, but maybe not as much affected by muscle mass like creatinine is. And then of course the urine, I think that sometimes we forget that urine is something very easy to look at.

not just a urinalysis, but then we'll look at a urine protein panel, look to see if the kidney is spilling protein in a way that it shouldn't be, looking at urine albumin, same thing, is the kidney spilling out albumin. Those signs of proteinuria, of albuminuria, those are signs or early signs that the kidney filter maybe isn't working as it should be. So kind of early clues for us that we should follow.

And then on the nephrology side, just like in the neonatal world, we love to trend. We love to trend numbers. We love to trend labs. So it's a lot of just subsequent visits looking at things like the creatinine overall trend, looking at the proteinuria, and of course, trending blood pressures along with it.

Daphna Barbeau (29:02.211)

Since we're talking about blood pressure, I actually have a question about our identification of hypertension in the NICU and how soon the nephrology team wants to be involved when we're working up those kinds of patients.

David Askenazi (29:21.66)

Yeah, I think for me, I would love for you guys to avoid ankle blood pressures because we don't really know what those mean. So upper extremity blood pressures that are consistently elevated is something that a nephrologist I think should be aware of. And then depending on the situation, the severity, we talk about treatment as well as additional...

plastics.

Daphna Barbeau (29:53.795)

Are there any other types of information you want us to collect before calling you? Do you want us to have gotten the ultrasounds or other laboratory data before we get you involved in the workout?

David Askenazi (30:05.116)

Yeah, I think that's a style issue. My style is before I start to dive into a workout, I want to just convince myself that it's real. And so if the baby is crying and screaming or they're checking the blood pressure in a way that's not optimal, I think the first thing to do is just to kind of verify that it's real. And then I start to work things out. So again, it's more of a style issue. If you're confident that you have really good blood pressures and that the nursing are documenting that,

babies calm when they're being checked, then certainly getting an ultrasound is a great place to start.

Ben Courchia MD (30:46.601)

So I wanted to maybe transition a little bit our discussion to the amazing work that is being done by the Neonatal Kidney Collaborative. I think Daphne and I are a little bit jealous of the Nephrology team because you guys have the best acronym for your studies, whether it is AWAKEN, NINJA. I mean, we're like in other areas. I mean, I'm consider myself maybe more of a long person because that's where my interest lies. But I mean, we do not hold...

Daphna Barbeau (31:04.003)

Agreed.

Ben Courchia MD (31:16.585)

We really do not come close to your ability as a group too.

David Askenazi (31:19.612)

Well, we recognize that marketing is important because there are so many lung researchers out there in neonatology.

Ben Courchia MD (31:22.633)

I'm sorry.

But I'm wondering if maybe you can tell us a little bit, especially you David as the president of the collaborative, what exactly prompted the creation of the collaborative? What is its mission and what is it really has achieved thus far in terms of making a difference for our patients?

David Askenazi (31:49.884)

Yeah, so thank you. So the collaborative is now 10 years old. It formed because we recognized that if we were going to make an impact, two things had to happen. Well, three things had to happen. One is that we had to change from a single center type of a model to a multi -center model to understand differences in practice patterns to increase sample size for us to kind of really understand epidemiology better.

The second thing that we recognized was that in order for us to really move the field forward, there has to be a partnership between neonatology and nephrology. So at our core, everything we do has a neonatologist and nephrologist associated with it. All our committees have both, all our papers have, most of our papers have first and last author who are neonatologist and nephrologist. So we recognize that. And then the third thing we recognized a decade ago was that

if we're going to sustain ourselves over the long run, we had to develop a board and governance and things like that, some infrastructure to kind of keep things moving forward. And our mission is really pretty clear. Our mission is to improve the outcomes of neonates who are at risk for kidney disease through research, education, and advocacy. And that's what we've done. And we have subcommittees for each of those three parts.

wonderful board of really dedicated neonatologists and nephrologists. And we're working to develop folks like Tara to kind of help provide mentorship for her as she's planning different projects. Recently we started an incubator, different than your incubator, but it's called the RINC, which is the renal incubator nephrology.

Something I forgot. It's an incubator for ideas.

Ben Courchia MD (33:47.881)

The name is, the name is still good. I mean, I'm sorry to say, and, and, and we're in Florida. They just won the Stanley Cup. So, I mean, this is perfect. I mean, this is a great acronym. I mean, what?

David Askenazi (33:54.908)

Thank you.

Yeah, right. So the RIC is a place where we want people to come together, share ideas, collaborate with one another. We're going to have some pilot feasibility grants that come from there. And the NTC really wants to promote young people, help them get started with mentorship as well as some projects. So that's recently started. And it's a volunteer organization that really just kind of

Daphna Barbeau (34:05.923)

Hehehe

David Askenazi (34:26.108)

emphasizes connection, emphasizing community, emphasizing belonging, and really trying to bring people together to do great work.

Daphna Barbeau (34:36.867)

I was hoping you could highlight some of the educational opportunities because the website, and we actually haven't mentioned it yet, it is babykidney.org, is really, I think, a wealth of information, even if you want to go into this field or if you're the bedside clinician managing patients. And so I think there's a lot to offer there. I hope you'll highlight some of those things.

David Askenazi (35:01.276)

Yeah, so we have some, so every year for the last three, four years, we've had sometimes one, sometimes three hour webinar that we bring in speakers and each will speak on a topic for 20 minutes. So those are all available on the website. We also have a section that outlines high impact articles in neonatal nephrology where you can kind of walk in and take a glance at it. And it's kind of like a mini abstract where you can

kind of read kind of the take -home message from the paper. We also are working to build some education material for families in that website. Those are kind of on the way. And we hope people kind of go there. If you have a topic that you want to cover on neonatal nephrology for your fellows, for example,

by all means, reach out to us. And one of us, if it's not on the website, one of us has one in on archives that we're happy to show.

Daphna Barbeau (36:09.443)

Yeah, I saw that you have a good opportunity for, for trainees, for early career people to also do some of those article reviews. Is that right?

Ben Courchia MD (36:09.705)

Sorry, I was.

David Askenazi (36:21.212)

Yeah, we encourage people to get involved. We find opportunities for folks to kind of be part of our organization at different levels. We have what we call the 6 -2 crew that Tara's been part of for residents or fellows interested in neonatal nephrology, where you essentially kind of spend some time in each of the committees and we find something fun to do, like a review of an article.

something from an advocacy perspective, with just little projects, but more really to kind of get you engaged with that organization.

Daphna Barbeau (36:59.491)

I love that. And you mentioned the virtual webinars, but we wanted to make sure we took a moment to introduce you have an international neonatal nephrology symposium this September. Can you tell us what you guys are hoping to achieve by bringing people together to talk about the kidney?

David Askenazi (37:17.5)

Yeah, so 10 years ago, there's no way anybody would have paid attention to a strictly neonatal nephrology symposium. When I first started, there was maybe four abstracts at PAS. Two were mine and two were somebody else's. And now there's 50, 100 abstracts on neonatal nephrology. So we felt like it was time to really bring people together to collaborate, to educate one another, to have...

to bring topics to light that are pertinent to the clinical arena, that are pertinent to the research arena in neonatal nephrology. And so we're really, really excited. It'll be a four day experience with keynote speakers, with fun social activities. And we'll have two pre -courses. One will be the RINC, which is kind of a research incubator for neonatal kidney disease. That's what the R stood for. And then we'll have one that is...

Daphna Barbeau (37:51.911)

Hehe

David Askenazi (38:14.652)

is on neonatal dialysis. We'll do a one and a half day course on neonatal dialysis prior to the INTS meeting.

Ben Courchia MD (38:24.009)

I wanted to ask Tara a little bit about your participation in the collaborative. I think that as a trainee, it always feels like you can interact by proxy, meaning you can just go through the channel of your attendings or your mentors, but you've really embraced the possibility of working as a true member of the collaborative. Can you tell us a little bit about that? What was the activation energy needed to make that leap? Because I know it's stressful. We all have a little bit of imposter syndrome.

happy have you been working with this amazing group of physicians.

Tara (38:58.094)

Yeah, thanks for the question, Ben. It is. It's been just an incredible experience. And I just wanted to emphasize the mentorship that's available through the NKC. So I actually found the NKC kind of serendipitously. I was actually looking at articles to help me come up with a fellowship project. And I stumbled across actually the website and a lot of the articles that were on there.

And I remember reaching out to Michelle Starr and Dave Sulewski had articles on there. They are two giants in the field of neonatal nephrology, as is David. And I asked them to have a meeting with me to discuss some ideas that I was having that were similar to a project that they were doing on fluid overload. And they met with me and they just, it took off from there. So I would just say to any trainee that's listening, I know that it can be really scary reaching out to people, but.

everyone in the field, especially in the neonatal nephrology world is just so eager to help trainees. And I think it just helps not to be shy and to just reach out. And I think I am a little fortunate in that those who know me know that I'm not really that shy to begin with. So it can be helpful to have that aspect when reaching out. But like David mentioned, the 6 '2 crew, it's sort of a cute name that comes from the 6 '2 gene, I believe it is, is the

Daphna Barbeau (40:02.755)

Mm -hmm.

Ben Courchia MD (40:03.049)

Hahaha

Tara (40:17.742)

embryologic kidney gene. David, if I butchered that, I don't, sorry, but so, so it just, it's sort of symbolic. Right? So it's, it's good, right? So, so just a kind of symbolizing these people who are sort of budding nephrologists. So through that, it's a rotating internship. We rotate through all the facets that the NKC has to offer through research. So I've done the research collaborative, which has helped, you know,

David Askenazi (40:21.596)

Yeah, it's pretty cool.

Daphna Barbeau (40:24.803)

That's cute. I like that.

Ben Courchia MD (40:26.217)

I mean, they're good.

David Askenazi (40:28.38)

It's a pluripotent. Yeah.

Tara (40:46.606)

allowed me to participate in review articles. Like David mentioned, we recently had this consensus meeting to come up with these kidney health assessment guidelines for NICU discharge. So it allowed me to be a part of that. Advocacy is a big one that I'm actually about to rotate through right now. And then of course, just education, which is educational opportunities like this.

like a podcast reaching out to both the nephrologists and neonatologists, but also educational opportunities for trainees to reach other trainees and talk about the work that's being done. So I just can't emphasize enough how important it is to find a group, whatever passion you're interested in, but like the NKC and just sort of, you know, go along for the ride there because there's a lot of mentorship to be had.

Ben Courchia MD (41:32.745)

And I wanted to maybe talk a little bit about your profile because I think we want to maybe focus the last few minutes of the conversation on the future of this field and get your thoughts on what you're excited about. But I wanted to just ask you one more question about your training because obviously you're taking your decision to pursue an area of expertise in neonatal nephrology could potentially change dramatically what

your role as a physician looks like. When we're thinking about this as neonatologists, we're very much quarantined to the NICU. Some of us do a little bit of follow up, but very few. But this additional training is allowing you to potentially create this new role where you would be in the ICU, you would be in the outpatient clinic. Can you tell us a little bit about how you envision your future and what kind of opportunities this is bringing for you that you're quite excited about?

Tara (42:26.734)

Yeah, so I guess I can't go through this podcast without mentioning my life and educational mentor, Dana Furman. So Dr. Dana Furman, she is a pediatric intensivist along with a nephrologist. So she's actually here at UPMC and is my primary mentor at UPMC. So what her career looks like and really what I'm looking to mimic is she does entirely inpatient time. So she does a majority of her time in the PICU.

but then is also on service for nephrology. And she also is our CRRT director or continuous renal replacement therapy director. So really I'm hoping to have a career just like that in terms of, you know, exclusively inpatient. At least I say that right now, but splitting my time working in the NICU.

Daphna Barbeau (43:12.419)

Mm -hmm

Tara (43:14.798)

but then also being available to be a critical care nephrologist particularly and be one that's consulted in the different ICUs, whether that's the PICU or the cardiac ICU, and help especially in the patients that need the CRRT.

Ben Courchia MD (43:29.897)

Mm -hmm.

Daphna Barbeau (43:31.958)

I was going to say certainly the sub -sub -specialist in neonatology, we're seeing more and more paths created in that way. So thank you for being a trailblazer. One of my last questions, David, is really, what do you think we have left to study about the neonatal kidney? What should we be looking for?

Ben Courchia MD (43:32.521)

before we go ahead.

Daphna Barbeau (43:57.187)

in terms of articles coming out in the next handful of years.

Daphna Barbeau (44:05.347)

Oops, sorry you're muted again, Dave.

Ben Courchia MD (44:06.985)

sorry.

David Askenazi (44:09.628)

Yeah, thank you for that question. We now have a pretty clear understanding that AKI is bad and impacts outcomes, fluid overload is bad and impacts outcomes. And I think that the next phase is really to try to decipher what pathways, what bundles, what systematic approaches that we have available today can we use to improve outcomes. Who should be screened? How should we screen them? What should we do about them?

So I think that's going to be an area that's going to be really exciting over the next few years. The other thing is, you know, that there's therapies available. There's data on aminophylline and caffeine. We haven't really learned how to use those well in any population, but clearly because they're so commonly used in neonates, we have lots of data from studies that suggest that they do improve clinical outcomes.

We haven't looked to see if they improve long -term outcomes, but that's something that I think definitely needs to happen. And then the work that people are doing with renal replacement therapy, I think it's still really early right now in the neonatal world. How do you assure that you're providing adequate nutrition? What can we do to prevent them from having complications during the therapy? And how do we develop a system where

It becomes more of a mainstream issue to address inability to maintain adequate homeostasis as opposed to a last ditch effort to see if we can save the baby. And that work has really evolved in the pediatric critical care arena into that kind of a mindset where it's organ support and not waiting until the last breath to intubate somebody.

but really providing support to the patient when the organ's not doing its job well. So those are things that a lot of people are working on. There's collaborations, there's registries. I mentioned some of the work that we're doing through the research incubator at the NKC. And I think that it's really exciting time right now to be in this arena.

Daphna Barbeau (46:32.515)

And since we're talking about the future, do you think we'll ever all agree on the right total fluid volume for babies?

David Askenazi (46:40.06)

Well, so here's the mindset of a nephrologist. I don't care what the TFI is. What I care about is nutrition. So give the patient nutrition and if they're swollen, then don't give them a lot of water. And if you can't accomplish both those things, then it's time to consider dialyzing.

Ben Courchia MD (46:49.865)

You

Ben Courchia MD (47:03.113)

I love that. This is great. Yeah. Because we begin this episode by saying that sometimes we make things too complicated. I think this is very easy to take home.

David Askenazi (47:15.452)

Yeah, fluid is fluid, calories are calories, and we got to unlink them when we think about critically ill patients.

Ben Courchia MD (47:26.953)

David, thank you so much for making the time to be on with us. Tara, thank you so much for joining us. Congratulations on a remarkable path that you're outlining. I am really hoping that people will take note of what you're doing and will shoot emails your way if people are interested in getting in touch with you to learn more about what you're trying to do. It was a pleasure to have this conversation. And again, we are going to refer people to the website of the Neonatal Kidney Collaborative.

babykidney.org, one of the easiest websites we had to advertise on the show. Thank you both for making the time to be with us today.

David Askenazi (48:04.988)

Thank you guys, really appreciate it.

Tara (48:05.358)

Thanks. Thanks so much.