#344 - Neonatal Nephrology - A Year In Review
- Mickael Guigui
- Aug 24
- 24 min read
Updated: Sep 6
Hello friends 👋
In this episode of The Incubator Podcast, we sit down with Dr. David Askenazi, Dr. Heidi Steflik, and Dr. Kimmy Vuong to explore the latest research and practice shifts in neonatal nephrology. The discussion begins with the often-overlooked role of the kidney in the NICU and why kidney health has direct implications for outcomes far beyond discharge.
The group reviews three recent high-impact papers. The first, a secondary analysis of the PENUT trial, examines whether PDA treatment in extremely low gestational age infants influences two-year kidney outcomes, raising questions about long-term renal risks and benefits of medical and surgical interventions. The second paper presents a consensus statement on kidney health monitoring for NICU graduates, offering structured recommendations on risk stratification and follow-up for preterm, critically ill, and cardiac infants. Finally, we highlight a quality improvement initiative that used the “Can You PLOTS” bundle to reduce ventilator days by addressing fluid overload systematically, underscoring the importance of early, proactive kidney-focused care.
This conversation emphasizes kidney disease as a critical factor in neonatal medicine, the growing pathways for neonatal nephrology training, and practical steps teams can take now to better integrate kidney health into NICU care.
Link to episode on youtube: https://youtu.be/p5hqk9d75L4
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Short Bios:
Dr. David Askenazi: Dr. David Askenazi MD is a professor in the Department of Pediatrics at UAB and 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. Additionally, 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.
Dr. Heidi Steflik: Dr. Heidi Steflik is an Associate Professor of Pediatrics the Associate Chief of Research, Neonatal-Perinatal Medicine and Associate Program Director, Neonatal-Perinatal Medicine Fellowship at Medical University of South Carolina. Dr. Steflik's clinical and research interests focus on providing life support to our sickest babies, as well as evaluating and treating kidney disease in neonatal patients.
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The articles covered on today’s episode of the podcast can be found here 👇
Condit PE, Guillet R, Kaluarachchi D, Griffin RL, Menon S, Askenazi DJ, Harer MW.BMC Nephrol. 2025 Mar 19;26(1):138. doi: 10.1186/s12882-025-04065-8.PMID: 40108500 Free PMC article. Clinical Trial.
Starr MC, Harer MW, Steflik HJ, Gorga S, Ambalavanan N, Beck TM, Chaudhry PM, Chmielewski JL, Defreitas MJ, Fuhrman DY, Hanna M, Joseph C, Kwiatkowski DM, Krawczeski CD, Liberio BM, Menon S, Mohamed TH, Rumpel JA, Sanderson KR, Schuh MP, Segar JL, Slagle CL, Soranno DE, Vuong KT, Charlton JR, Gist KM, Askenazi DJ, Selewski DT; Neonatal Kidney Health Consensus Workshop.JAMA Netw Open. 2024 Sep 3;7(9):e2435043. doi: 10.1001/jamanetworkopen.2024.35043.PMID: 39269711 Free article.
Askenazi DJ, Gordon L, Griffin R, Collins M, Black A, Ambalavanan N, Webb T, Mathis M, Short K, Umberger A, Travers C.Pediatr Res. 2025 Jul 11. doi: 10.1038/s41390-025-04078-x. Online ahead of print.PMID: 40646283
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The transcript of today's episode can be found below 👇
Daphna Yasova Barbeau: Hello, and thanks to all who have been following along in our year in review series. Today, we're going to tackle the topic of neonatal nephrology. And today I have the pleasure of having on Dr. David Askenazi, Dr. Kim Vuong, and Dr. Heidi Steflik.
Dr. David Askenazi is a professor in the Department of Pediatrics at UAB, and he was appointed the inaugural W. Charles Mayer Endowed Chair of Pediatric Nephrology in 2021. He founded and is currently the medical director of the Pediatric and Infant Center for Acute Care Nephrology at Children's of Alabama. Additionally, he founded and currently serves as the board chair of the Neonatal Kidney Collaborative. You can find them at www.babykidney.org. He is also the chief scientific officer for Zorro-Flow Inc.
Dr. Heidi Steflik is an associate professor of pediatrics, the associate chief of research, and the Associate Program Director of the Neonatal Perinatal Medicine Fellowship at the Medical University of South Carolina. Her clinical and research interests focus on providing life support to the sickest babies, as well as evaluating and treating kidney disease in neonatal patients.
And Dr. Kimmy Vuong is joining us as a clinical fellow from Baylor College of Medicine. I'm so excited to speak to her more specifically about her unique path. So good morning, Dr. Askenazi, Dr. Vuong, and Dr. Steflik. Thank you so much for joining us today. We're so excited to hear all of your expert opinions on these very high-yield neonatal nephrology papers. You selected three papers that I think were a great representation of what came out in the last year. But as everyone's anticipating these neat papers, which I'll introduce in just a second, I want to get everybody's gears turning. I'll ask you, Dr. Askenazi: why is it so important that we pay attention to the kidney in the NICU?
David Askenazi: First, thanks for highlighting neonatal nephrology in your podcast. I know this is viewed by people from all over the world, so we're very excited and thankful that you're highlighting it.
For those who don't know, the kidneys are in babies and they are important. And when the kidneys aren't functioning or doing their job well, then it's really up to us as providers to help the patient maintain homeostasis, remove toxins, and do the job of the kidney for them. Over the last decade or two, we’ve shown that not only is kidney injury associated with poor outcomes, but so is fluid overload. One of the challenges we face is that it can be very complicated to talk about the kidney. I'm on a quest to try to simplify things for everybody so that we can all get on the same page and do the best for our kids. Kidney disease matters. Kidney disease matters in the NICU and beyond.
Daphna Yasova Barbeau: I love that. I feel like neonatologists think the kidney is this independent organ that we have to manage. But I think these papers highlight that the kidney impacts many, potentially all, of the disease processes we see in the unit. We just can't manage one independently of the other. Dr. Steflik, how do you think that changes your management in the unit?
Heidi Steflik: Yeah, absolutely. Until fairly recently, neonatology is still a pretty young field in medicine, but until the last decade or so, the kidney has been largely overlooked. When we notice that the kidney is having a problem functioning in the NICU, it often looks like a temporary problem and often resolves on its own because we lack specific therapies to support the kidney well in the NICU. But we’re finding with some of these articles—and some of the future directions we all have in mind—that insults in the NICU are really going to have lasting impacts for many of these babies. We need to be thinking about that even when they're premature in an isolette in our NICUs, because these lasting impacts may affect the rest of their life.
So it's really important that we approach the patient holistically—not just focusing on the kidney, or the PDA, or the lung disease, but really looking at all the interactions that we know are there and that we’re learning about every day.
Daphna Yasova Barbeau: And the kidney is so important that it has its own fellowship. Dr. Vong, tell me a little bit about the neonatal-nephrology fellowship. You're a pioneer. What does that look like? What’s the process like? Maybe others will get their interest piqued as well.
Kimmy Vuong: Yeah, definitely. I certainly hope so. I'm one of a handful of trainees doing dual training. I already finished my pediatric nephrology fellowship here at Baylor College of Medicine and Texas Children’s. Then I was grateful to stay on for a two-year NICU fellowship. Most of us have done one fellowship first, then decided we love the neonatal nephrology space, and chose to pursue another two-year fellowship. I do know of one trainee who came in intending to do a combined track. So there are ways to do it if you’re mission-driven and passionate.
We’ve had a lot of undergrads and med students reach out to me and talk about exploring this area. I think we’re at the very beginning of what hopefully will be a pipeline for more specialized neonatal nephrologists. And we’ve got giants in the field like Dr. Askenazi and Dr. Steflik who can lead the way and help us grow into our own little niche group.
Daphna Yasova Barbeau: I love that. I think that's so exciting. And I think there are already some neonatologists interested in the kidney. Will there be a pathway for people who have already done a neonatal fellowship to specialize in neonatal nephrology?
Kimmy Vuong: I think we’re already seeing it. That’s how this field came to be—people followed their passions. Even if they didn’t have board-certified training in the other specialty, they knew enough, were passionate enough, and directed their free time and research into that space. They became the experts without extra training.
For people like me earlier in training, it’s a great opportunity to get that exposure. Having the nephrology lens in the NICU makes my perspective different. When we talk about managing babies, there’s so much organ crosstalk. I’m always thinking about fluid balance and kidney stress, even before injury happens. It’s been really cool to see how my perspective differs from my co-fellows, and to learn from them too.
Daphna Yasova Barbeau: Well, let me introduce the papers and then we'll jump right in. You selected three papers. The first is from BMC Nephrology: “Association of PDA Treatment and Extremely Low Gestational Age Neonates with Two-Year Kidney Outcomes a secondary analysis of the preterm erythropoietin neuroprotection trial (PENUT).” The second is from JAMA Network Open Pediatrics – “Kidney Health Monitoring in Neonatal Intensive Care Unit Graduates: A Modified Delphi Consensus Statement.” The third is from Journal of Pediatric Research, “Reducing NICU Ventilator Days by Preventing Fluid Overload with the CAN-U-P-LOTS Standardized Bundle.” And I think that last paper wins best mnemonic in a title! Where would you like to get started?
Kimmy Vuong: I can start. So for my article, I have The Association of PDA Treatment in ELGANs with Two-Year Kidney Outcomes: A Secondary Analysis of the PENUT Trial. I love all the secondary analyses that came out of this PENUT study. I think it shows us a lot about different data points and long-term outcomes to consider in this population. This one just came out within the last month, so I was very excited to read the newest information about this cohort. The objective of the study was to assess whether treatment of PDA in ELGANs affects kidney function, specifically eGFR, proteinuria, and blood pressure. They chose the two-year time frame because renal maturation is supposed to be complete by then.
This was a secondary analysis of the multicenter randomized controlled PENUT trial, which included 19 academic centers and 30 NICUs in the US. The ELGANs were 24+0 to 27+6 weeks gestation, enrolled within the first 24 hours of life, and had either arterial or venous access. They excluded babies with major life-threatening anomalies, hematologic crises, hematocrit >65%, hydrops, and congenital infection.
The primary aim was to look at whether PDA treatment impacted kidney function. They defined low GFR as <90 mL/min/1.73m², using the CKiD U25 equation (Chronic Kidney Disease in Children under 25) equation, which incorporates both serum creatinine and cystatin C. They defined albumin-to-creatinine ratio >30 mcg/g as abnormal. For secondary aims, they looked at systolic and diastolic blood pressure >90th or >95th percentile, and associations between specific PDA medications and kidney function.
In total, 606 ELGANs had two-year follow-up data. Of these, 57% had treated PDA (pharmacologic or surgical), 43% had no documented treatment. Of the treated group, 64% received medical therapy (mostly indomethacin), 5% surgical, 22% both, and 9% unspecified. Importantly, medications given in days 0–3 were excluded since those were assumed to be for IVH prophylaxis.
When comparing treated vs. untreated groups, PDA-treated infants had lower gestational age, lower APGARs, lower birth weight, length, and OFC, as well as higher rates of BPD, NEC IIA stage or higher, sepsis, and vasopressor use. They adjusted for confounders for in regression analyses.
In terms of results, they found that there was no significant differences in albumin-to-creatinine ratio or eGFR overall. Infants treated for PDA were less likely to have systolic blood pressure >90th percentile at two years (aOR 0.59). Indomethacin or combination therapy (day 4–28) was associated with higher rates of low GFR at two years, compared with acetaminophen or ibuprofen. Then, to look at shunt burden, they saw that delayed surgical closure (>30 days) trended toward higher risk of low eGFR, but not statistically significant (p=0.08).
Strengths of this study include that it was a large multicenter cohort, prospective data, intentional follow-up at age 2. Limitations are that it was a secondary analysis (not randomized PDA treatment), variation across sites, lack of detailed echo/hemodynamic data, one-time kidney assessment (no longitudinal outcomes).
Overall, I really enjoyed this article. It highlights trade-offs in PDA management. NICU therapies can have long-term consequences we don’t always see until childhood or later. This paper teaches me a lot about the trade-offs in the big picture about treating a PDA, especially hemodynamically significant PDA, versus conservative management. Especially in this very high risk cohort of ELGANs who are already born with a very low nephron mass, injury to the kidney, less reserve than an older baby. From the nephrology side, I really think about the long-term monitoring. What are different metrics that these primary care physicians need to look at? How can we provide support for them? How can we make sure that the follow-up is there, even once they leave our high-risk infant follow-up clinics? We don't want these babies to just kind of get released out into the world and there's no information for their parents or for their providers about what the next steps are. I also think it speaks to some of the consequences of some of the therapies and management decisions that we make in the NICU and how a lot of those consequences, they might not even appear until early childhood, sometimes adolescence. And so how can we make sure that we're talking to families about these long-term risks so that they can have healthy, full adult lives too, and not just surviving to NICU discharge.
I’ll also plug a great perspective piece in the Journal of Perinatology by Kim Reidy: Advocating for the inclusion of kidney health outcomes in neonatal research: best practice recommendations by the Neonatal Kidney Collaborative. We need to intentionally design studies that consider the kidney—not just lungs, PDA, or neurodevelopment.
Daphna Yasova Barbeau: Thank you. What an excellent review of a complicated paper. Obviously, the PENUT trial has given us so much information. I love the term you used—the “trade-off.” Especially in this cohort, it’s interesting that we saw both decreased GFR and less systolic hypertension. Dr. Askenazi, what does this really mean for babies? Is it worth the trade-off?
David Askenazi: That’s a tough question. The question of how to address PDA has been debated for decades, and I don’t know if anyone fully understands the best approach. What I think Kimmy and this paper bring to the table is: if there’s no difference in lung outcomes or other outcomes, maybe the kidney can be the tiebreaker. If one approach to PDA has long-term consequences on kidney function, that could influence how neonatologists make decisions. We’re still early in the field, but the kidney needs to be one of the jurors in this debate.
Heidi Steflik: I really applaud Paige Condit, Matt Harrer, and Dr. Askenazi for tackling this study. There’s a lot happening this summer in the PDA world: the JAMA meta-analysis was published in May, the new AAP clinical report just came out, and the pendulum is swinging toward avoiding treatment in the first couple weeks of life. But those recommendations are largely based on composite outcomes and BPD. While those may be stronger drivers, as Kimmy introduced and Dr. Reidy’s article emphasizes, we can’t forget the kidney when making these decisions or designing new studies like the ongoing NRN trial.
Daphna Yasova Barbeau: Yes, I love that. What's so interesting about this paper because it was a secondary analysis, but there are specific concerns, I think, in the unit clinically when we're treating a PDA medically—not just about the flow to the PDA, or the lack thereof after closure, but specifically the medications used for treatment. And obviously in this cohort, indomethacin was the most commonly used medication, or multiple medications were used. I think as a community we're moving a little bit away from indomethacin, even when we are choosing to close the PDA. Obviously, we don't have that information, but do you think the findings might look different if Tylenol was the primary medication used?
David Askenazi: Most nephrologists—neonatal or otherwise—will say: if you know someone has low renal function or low reserve, use Tylenol first. Doesn’t mean you can never use ibuprofen, but NSAIDs are nephrotoxic, and if you can avoid them, it’s better for long-term outcomes. I’d love to see data comparing long-term kidney outcomes with Tylenol versus indomethacin.
Daphna Yasova Barbeau: And all ELGANs have a high risk kidney profile. And then Dr. Vuong, I'll let you finish. I took your point to heart—that we're going to have to start evaluating the kidney as an outcome for a lot of studies. How do you think this paper models for people who want to include renal outcomes?
Kimmy Vuong: Yeah, thank you so much for that question, Daphna. I think this paper is a good model for really thinking about that data point and being intentional about what type of information you're collecting. I loved the use of blood pressure, eGFR with that specific equation, and the albuminuria cutoff. It's helpful, clear, and provides consistency across sites. Many centers might not otherwise have done a urine test on these kids at two years of age, so this kind of helps providers and gives them guidance on the exact metrics to assess. How do we define kidney dysfunction, damage, or risk at that time point? Having those conversations before the study even launches gives researchers a good toolkit for knowing how to assess it. And I think Heidi’s article will talk more about good time points for assessing NICU graduates long-term, and some things we can do outpatient, even when neonatologists aren’t the ones following the baby, but our great primary care providers are.
Daphna Yasova Barbeau: Thanks so much. And then I understand, Dr. Steflik, you’ll take the next paper—is that right?
Heidi Steflik: Yeah, that’s a great segue, Kimmy. Thank you.
Dr. Askenazi, Kimmy, and I were all fortunate to be part of an NIH-sponsored workshop back in February 2024, called the Neonatal Kidney Health Consensus Workshop. This was funded by an R13 written by Dr. Michelle Starr at Indiana. She’s brilliant, and we’re so lucky to have her in our field. She sponsored this with the NIH, and we all congregated to ask: what do we do for these kids when they leave the hospital? We worry about them during hospitalization, but what about after? There’s no guidance, no guidelines, no consensus statements about long-term kidney health or screening for NICU graduates. We wanted to change that and at least get something on paper, recognizing it would need reiteration and refinement.
So we divided into three work groups: preterm infants, infants in the NICU (not necessarily preterm) with AKI or other high-risk exposures (e.g., ECMO), and infants with critical congenital heart disease. We’d work in groups and then reconvene in the afternoons using a Delphi approach to approve recommendations. Ultimately, we published a paper with 10 recommendations: three overarching (for any at-risk NICU graduate), two for preterm infants, three for critically ill infants with AKI, and two for infants with congenital heart disease.
The recommendations focus on assessing risk at NICU discharge—asking, are they at risk, or are they high risk? For example:
Preterm infants: most preterm/VLBW, or those with AKI, were high risk.
Critically ill: babies requiring dialysis or recurrent/severe AKI were high risk.
Cardiac: babies with severe AKI, daily nephrotoxic exposure, major surgery, or single ventricle physiology were high risk.
At discharge, the team and family should be reminded about kidney health—avoid NSAIDs if possible, use Tylenol first, etc. We also recommended comprehensive kidney health assessments at varying time points across the first two years: ongoing education, creatinine or cystatin C, GFR estimation, urine albumin/creatinine ratio, maybe ultrasound, depending on resources.
We know resources differ worldwide, even across the U.S., so sometimes this will happen in the pediatrician’s office, sometimes nephrology, sometimes in partnership with cardiology.
We’re really excited. This is just a starting point, but it gives us important questions for future study. I was proud to be part of it, and excited that we’re all thinking long-term about kidney health.
Daphna Yasova Barbeau: Yeah, I think this is so critical, Heidi. There’s beautiful graphic really about the consensus recommendations by the risk assessment during the initial hospitalization, the preterm infant, the critically ill infant with AKI, and the infant with critical cardiac disease. It goes by what their outpatient follow-up looks like, by the six month, the 12 month, and the two year follow up. I thought that was really helpful and very easy to follow. I think it can help how we provide anticipatory guidance for families.
I was surprised because we use a lot of renal imaging in the neonatal unit to assess the kidney. But really, it looks like the renal ultrasound may have been the least useful thing that you were recommending. You recommended a lot of urine studies. Tell me a little bit about that.
Heidi Steflik: Yeah, Dr. Askenazi is the expert on many of these things, of course. But the renal ultrasound, unless there is CAKUT (congenital anomalies of the kidney and urinary tract), severe urinary tract dilatation, VUR reflux, or anatomical problems, we're really not sure what information from the renal ultrasound we can use for this guidance of long-term kidney health. It's still a question mark for us. That was one of the other pieces of the paper that's published that final table there for anybody who's listening that might be interested in becoming involved in neonatal nephrology and doesn't know where to start. We posed a lot of the gaps. We said out loud, these are the problems. We don't know what to do with the renal ultrasound quite yet in many cases. And so we identified those gaps and we talked about opportunities and what we think maybe the next steps are in our science as we're trying to push the field forward.
To your point about using urine studies, we're using cystatin-C in the outpatient space quite often for the eGFR estimations. Even in the NICU and in cardiac ICU, the future is coming where we're really going to be utilizing those urine studies and some novel biomarkers. NGAL, for example, is one of the ones that I know has been the subject of METCH study. We're still just not exactly sure how to harness that technology and how to use it appropriately in a NICU. Wouldn't it be great to know ahead of time that a baby was getting sick? Or that NEC is coming? And if there's abdominal pathology, perhaps the kidneys being influenced. So we're still asking those questions and learning the best ways to utilize those tools in the NICU, but I think it's definitely coming down the pipeline. Dr. Askenazi, do you have other thoughts about that or comments?
David Askenazi: The whole purpose of the consensus guidelines were to really find the minimum acceptable places where we can identify that a baby needs to be closely monitored or get therapies. What we're proposing is that somebody check the baby periodically.
One of the time points that we thought was really important is right before they go home. So just like you do car seat check to make sure the baby's going to be okay, we think that before they go home, they should have sunscreen because if they have hypertension or chronic kidney disease before they go home, then they need someone to watch them a little bit more carefully.
In the outpatient arena, we just wanted to kind of set clear, reasonable things that most pediatricians or nephrologists would agree need a higher level of vigilance. So as Heidi said, blood pressure, elevated protein, and elevated creatinine are important to monitor.
And if you look into that paper, there is so much that's unknown about this topic. When you really step back and ask fundamental questions like, what does a creatinine mean? It is not as specific as people think it is. It is a very crude estimate of kidney function. And even in people who have a normal creatinine, remember, you can have a solitary kidney. So you can lose 50% of your kidney and have a normal creatinine. That doesn't mean you're normal. That doesn't mean you're not at risk to have long-term kidney disease. We have very crude instruments to understand kidney function right now. And I think things like novel biomarkers that can detect whether someone is having ongoing fibrosis or ongoing inflammatory processes that are not allowing proper repair or growth are very important. We don't have those quite yet. Understanding what the true kidney function is and what the true kidney function reserve is, we don't have those yet. To understand how much kidney nephrons or how much kidney function someone truly has, we don't have those yet. I think that those will come over the next five or so years to improve kind of our ability to screen babies in the NICU to say, “I know this kid's at risk” versus “this guy has a creatinine that looks a little elevated, but it's not really a problem.” So we're really kind of working with crude diagnostic tools that are going to get better.
Daphna Yasova Barbeau: I love that. One of my big takeaways was the discharge checklist for evidence of ongoing kidney disease. So: serum creatinine greater than or equal to 0.5 milligrams per deciliter, the BP greater than the 95th percentile for age, hypertension already being treated with medications, or known nephrocalcinosis - I think that gives us all something to work off of and being sure that like for those babies, at least the nephrology referral sounds absolutely critical.
David Askenazi: Yeah. Another thing our team really focused on was we didn't want to overburden the system with saying, everybody needs assessments every three months. We really looked at what was the evidence to drive the assessments that we thought were appropriate. For example, in most preemies, what they really need is blood pressure checks throughout their first two years, which has been recommended by the AAP for a decade, even though very rarely followed. We also need a good two-year assessment of what's your kidney function, what's your blood pressure, and your urine. So we were very careful not to overburden the system with multiple time points in checking for different things. We just put out what felt like the right balance between monitoring but not overburdening.
Kimmy Vuong: I was going to add, jumping back to your question previously, I think this article that Dr. Steflik just presented can give a good model for other studies in terms of different time points, what metrics they're using to assess that kidney. And I think the more that we do this, especially at consistent time points with consistent measures, like we're always getting a cystatin-C, we're always getting a blood pressure, we're always getting this and that, we can start to pool information across multiple studies. I think the consistency that we have as a field of neonatal nephrology, I think over time, even if our ends are small within each of these studies, we'll be able to kind of see the greater picture a little bit easier. And so I think Dr. Steflik's article is a good one to hopefully serve as a reminder or as an example for people who are designing clinical trials down the road.
Daphna Yasova Barbeau: Thank you for that. And we have one more paper that I think will spark a lot of interest. Dr. Askenazi, you’ll finish us off with the last paper – “Reducing NICU ventilator days by preventing fluid overload with the CAN-U-P-LOTS standardized bundle.”
David Askenazi: This has been a really fun project so far. This was started in the halls of the NICU where I was frustrated with why they were waiting so long to call us to help manage a very swollen patient. We know from some studies that specifically in the NICU, compared to the pediatric ICU, the cardiac ICU, or the adult ICU, there’s a tolerance for allowing much higher degrees of overload or fluid balance before people start to address it.
So what we did was get together with the neonatologists and nephrologists at our institution and asked, why do we have to wait so long? Maybe we can start to implement a systematic approach even before the nephrologist needs to be called. We came up with a list of things that were easy to assess and had potential interventions to go with them. Those were the two things we wanted for each element of the bundle.
We proposed it to our team, then designed a quality improvement project: we gathered baseline data, had a one-month washout period where we trained nurse practitioners and physicians in both neonatology and nephrology, and then observed what happened after implementation.
We tried to come up with a good marketing name, and we came up with “CAN-U-P-LOTS.” Colm Travers, the neonatologist I partnered with, wanted the first element to be “C,” which stands for Cause. His argument, which I fully agree with, is that there are many different reasons why people can develop fluid overload. If you don’t stop to think about the underlying cause, you’re missing half the story. Management is very different for a patient with heart failure versus intravascular depletion, compartment syndrome, or nephrotoxic AKI.
C: Cause – think about the underlying reason for overload.
A: Albumin – ensure enough oncotic pressure. Very debatable, but we set thresholds for giving concentrated albumin, despite limited evidence. Studies show 5% doesn’t increase your oncotic pressure much. So we recommend giving concentrated albumin if the albumin level is 2-2.5.
N: Nephrotoxic meds – just avoid fueling the fire.
U: Ultrafiltration (meaning dialysis). The whole point of the bundle is actually to prevent the need for dialysis. If we can address a high-risk patient with a systematic approach, our hypothesis was that you can reduce the need to call us to bring the machines in. U also stands for Uric acid. There are studies that show that if you have a very high uric acid level, it causes crystallizations of the collecting tubules, which then causes further kidney injury, and it's a positive feedback cycle. So patients who have a very high uric acid get treated with Rasburicase.
L: Lasix stress test. The idea is, don't just give diuretics willy nilly. Be really mindful about them. If you give Lasix and you have a really good response, it's basically telling you that the system is intact – it doesn’t mean you need more diuretics. It means that this kidney is functional and you should think about it. For example, if I'm dehydrated and you give me a diuretic, I'll pee more. But that doesn't necessarily mean that I need more diuretics. It just means my tubules are able to see the diuretic and will make me pee more. Alternatively, if you give me a big dose of diuretics and I don't make extra urine, then it tells me that something's wrong. Maybe there's an obstruction. Maybe there's tubular injury. Maybe you don't have enough oncotic pressure to bring the diuretic into the tubular cells.
O: Output/Obstruction – ensure adequate urine output and no obstruction.
T: Total fluid intake – For patients who are fluid overloaded, there's no reason to give dilute fluids. So concentrate medications, nutrition, and blood products as much as possible.
S: Steroids – Just like nephrologists, when we have a patient that we don't know what to do, we give steroids, so do a neonatologist. Colm wanted to throw that in there, to remind people that sometimes steroids are important for maintaining blood pressure
After implementation, we saw about a 20% reduction in ventilator days, similar reductions in oxygen days, and shorter NICU stays. Of course, it’s a single-center study, but I think it’s proof of concept that being systematic and proactive can improve outcomes.
Daphna Yasova Barbeau: I love that. The paper really caught my attention because, at the bedside, when you recognize fluid overload, you often think, “Did we think about the kidney?”—and by then it can feel too late. This paper underscores how much there is this interplay between fluid balance, especially when we're talking about the lungs and the need for ventilators and oxygen and long-term lung disease. This checklist makes it easy for us. I wonder, at what point do we enlist the CAN-U-P-LOTS bundle? Can we use it to prevent fluid overload in the first place?
David Askenazi: Neonates are tricky because they may look fine for weeks and then suddenly get sick. In other populations, like pediatric sepsis or cardiac surgery, bundles like this are used proactively for patients at risk for developing edema. We’re not saying a patient in shock doesn’t need fluids. We’re saying be mindful: track cumulative fluid balance, think systematically about causes, and intervene before they’re so swollen that it’s hard to make progress.
Which babies should we focus on? Not every NICU patient—probably one in 10 or 12. The high-risk ones: major abdominal or cardiac surgery, critical sepsis, documented AKI, worsening fluid balance, compartment syndrome, tense abdomens, NEC. Those are the patients we should target.
Daphna Yasova Barbeau: Thank you. I really liked your discussion of the Lasix stress test—just because a baby responds doesn’t mean diuretics are what’s missing. I was also interested in the uric acid monitoring and more careful use of albumin. Concentrating fluids is such an important point. In our unit, we were good at tracking medication volumes but not as good at monitoring flushes—how much, how concentrated, how often. What are some other “hidden” ways babies might be put at risk?
David Askenazi: One of the most important is remembering that TFI is not nutrition. In a healthy baby, yes, nutrition is prescribed through total fluids. But in fluid-overloaded patients, you must separate them: prescribe nutrition for calories and protein, then deliver it with as little fluid as possible.
Another point I missed earlier: P is for Pressure. Renal perfusion is not just about mean arterial pressure—it’s also about venous pressure and abdominal pressure. If a patient has a lot of fluid in the tank or has abdominal compartment syndrome, you may need a higher MAP to perfuse the kidneys. So perfusion in our bundle is not just about a number, it's really about pushing the MAP up to overcome resistance and assure that there's plenty of renal perfusion. So you can have someone that with a normal lactate and a capillary refill of two seconds, but their BUN/creatinine ratio will be going up and the urine output will drop until you get that renal perfusion.
Daphna Yasova Barbeau: Love those pearls. My big takeaway is that the bundle was associated with reduced ventilator days, length of stay and mortality; those are things we already know fluid overload worsens. So having a tool to prevent it is really exciting. Thank you all for the work you’ve done to make it simple and streamlined.
As always, I’ve kept us overtime. Do you have any closing thoughts?
Kimmy Vuong: As the trainee here, I’ll just say I’m excited to be in this space. We’re standing on the shoulders of giants like Dr. Askenazi, Dr. Steflik, and many others. I’m grateful to share our love for kidneys and babies, and I hope more people join the field. It’s a great community. We are very welcoming, so please get involved.
Heidi Steflik: A great way to get involved is through the Neonatal Kidney Collaborative (NKC), now an official nonprofit. We have intensivists, nephrologists, trainees, medical students, and even patient families. Our goal is to improve kidney health for babies. You can find us at babykidney.org with contact info for all three of us. Please come join us in neonatal nephrology.
David Askenazi: Thank you again for having us. My message is: there are things you can do today to improve kidney care. From programmatic changes to better systems, to engaging colleagues. There's a lot of people available to kind of help you and people that have walked through these types of issues – like how do I engage with my neonatologist or my nephrologist? How do we develop programs to prevent kidney injury in our NICU? How do we use biomarkers? How do we develop a long-term follow-up? There's people that have done it. Please reach out to your friendly nephrologist, neonatologist, one of us, and do something. You're not going to be able to do everything tomorrow, but get together with your team, find partners in your hospital, and address one or two of these things that we've been talking about.
Daphna Yasova Barbeau: Perfect. This spirit of collaboration and small steps is exactly what I’ve seen in the neonatal-nephrology community—friendly and easy to work with. David, Heidi, Kimmy, thank you so much for joining us today.
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