Rethinking Kidney Support Therapy for Neonates with Congenital Kidney Failure

So it's my distinct pleasure to introduce our next speaker, Doctor Askenazi, um, is the W. Charles Mayer Endowed Chair of Pediatric Nephrology, um, and the Director for the Pediatric and Infant Center for Acute Nephrology at the University of Alabama in Birmingham and Children's Hospital of Alabama. Um, he has been an amazing resource for our center, um, as we have started using modified aquaphoresis as an option for, um, early dialysis and, uh, some of our neonates with in utero renal failure. So Doctor Askenazi, we're really excited to hear your perspective, um, on the care of these infants. Great. Thank you so much for the really wonderful kind introduction and uh for really allowing me to participate in what is an incredible uh session that you guys are doing. So thank you for helping me be, uh, allowing me to be a part of this. Um, can you guys see my slides here? Let's see. You guys see my slides, OK? Yes, thank you. Yeah. Great. So, um, so my perspective that I'm gonna share with you today is to recognize that things are changing and that, um, the way we look at outcomes in, uh, in patients who have kidney failure in utero. Um, probably needs to change because the, the way we're helping these babies are changing. And so the, what we can do outside of the uterus is changing and so our outcomes, uh, are gonna change not only based on what happens, uh, in utero with these amnio ports. and amniocentesis and the care that we provide them in utero, but also what happens after. So, hopefully, this will help you, um, rethink um how kidney support therapy, this, uh, I use that synonymously with dialysis, um, can help, uh, these babies with congenital kidney failure. A couple of disclosures I have to, to tell you about is that I do consult and receive funding from companies that make machines that we're using. Uh, some of these are not FDA indicated, uh, as they're, uh, uh, for, for small children. Um, I do have a couple of inventions, and I'm going to be showing some pictures, um, stories of real patients, um, their families, uh, not only give me permission, but encourage me to talk about this, um, them in these types of settings. So, um, in the next 20 minutes or so, I hope to review some of the registry data on, um, the survival of infants requiring congenital, uh, requiring dialysis for congenital kidney failure. Um, I will, um, tell you that those are, uh, a little bit old registries, so we'll put those in context. Um, talk a little bit about what kidney support therapy is and how that has evolved over the last 5 years at our institution. And with those, I think it, uh hopefully, Help you guys, um, think about why our approach to clinical decision making, family counseling, and, uh, our collaborations, uh, must continue to evolve with these advancements because things are, uh, moving quickly. So, I'm gonna present you with a case. Uh, this is a, um, a, a, a neonate that had a bladder outlet obstruction, uh, diagnosed in utero, uh, was born at around 3 kg, and, um, on day one, the patient was intubated, placed on a high frequency oscillator ventilation, and, um, the lungs were small and had pulmonary hypertension. Um, and so, uh, that was not able to support the baby with just a ventilator, so they put the baby on ECM. At that point, they called nephrology. I was not on. It was one of my colleagues. Uh, and our nephrologist basically was shocked, said, we can't do this. No one's ever done this. Uh, what do you mean we're gonna try to save this baby who's on ECMO? Their lungs are too tiny. It's not gonna work. Are you sure you wanna do this? Um, and so, after a long discussion with the family, Um, the family wanted to proceed. The neonatologists were, um, very, um, uh, optimistic that we could do this, and so we started dialysis via the ECMO circuit. When the ECMO was no longer needed, we switched over to the Aquadex, um, with a seven French temporary catheter. Um, at day 10, the patient was able to come off pressors. On day 14, was able to come off the ventilator. Still required a lot of medications for pulmonary hypertension. Uh, we were able to wean those off by around 4, 4.5 months, came off CPAP. Um, and, uh, more of the story is that this baby ended up going home, and after, um, 10 months, came off dialysis, surprising to us, uh, had enough kidney function to sustain himself. And, uh, he's now, you know, 2 years old, and he's waiting on the kidney transplant list with severe kidney disease, but not needing dialysis. Uh, he's a beautiful baby. His lungs are As far as we can tell, uh, doing very well. He does not need oxygen. He's had a couple of respiratory infections, and, uh, he's doing great. So, We said, OK, well, that was one case. Maybe that's just kind of an anomaly. So, a couple of months after this baby was born, I was on service and we were called because there was a baby who's being transferred to our hospital, who had um, um, a similar story, 2700 g birth weight, 36 weeks gestational length, had severe kidney dysplasia with oligohydramnios. Um, and the baby was intubated, was put on ECMO, and, um, and they called us after this baby was on ECMO with severe kidney failure, not making any urine at all. So they called us and I, and I said, you know, listen, are you guys sure this is what you want to do? Um, after a conversation with the family and with the neonatology team, uh, the family really wanted to do this because they've had, you know, very difficult time having a, a child. So they were, they were in it to win it. And so, This baby was on ECMO on Day of Life 2, was able to come off ECMO after about a week, um, had a gastric perforation, so it made, uh, the possibility of peritoneal dialysis impossible for a while, and we, uh, went ahead and started, um, dialysis with the ECMOs, I mean, with the Aqueduct circuit. Um, this is how she evolved. At 4 months of age, she was extubated, uh, to CPAP. At 5 months, we stopped CPAP. Um, she came off oxygen after a few months after that. Um, we, you know, discharged her home on hemodialysis because PD was not possible. Um, at around 10 months of age, we, we, we did d peritoneal dialysis, and she, she was able to, to grow and do well. And I got a kidney transplant at 22 years of age. Um, this is a 3rd case, uh, kiddo, very similar story, started life on ECMO, extubated at 1 month of age, um, and is doing great at home on peritoneal dialysis, requiring just a tiny whiff of oxygen, uh, at night. So, These 3 cases, and we've had 1 more of a patient that started life on ECMO have really um shocked us, uh, because the idea was, look, if their lungs are too little, there's nothing you could do about it. And I think the, the message to, to me is that if you can support them and get them bigger and provide them nutrition and get their lungs to grow, um, and, um, and avoid, uh, uh, problems during the NICU, these babies do have a chance to live. So, I'm gonna step back and uh talk a little bit about some of the registry data. This is registry data from uh Europe, um, that looked at patients from 1991 to 2013, 1000 patients who were in this registry from uh multiple countries across the world. And what you can see is, um, that 80% of them at 5 years survived. These are babies that were put on dialysis within the first year of life. Um, so their survival is actually pretty good, uh, around 80%. Uh, 5 year survival. Um, this is, um, similar data from 264 patients from Australia and New Zealand, um, that, uh, again shows similar And you could see the mortality rate um in black of about 20%. Uh, you could see that most of these patients are transplanted by 5 years of age, um, and about 20% continued in the white, continued to be on dialysis, um, at 5 years of age. And then a US data registry, uh, from compared outcomes between uh the 1990 to 1999, decade versus the 2000 to 2014 time point. And what I want to point to is that the survival rate has improved. And so, as opposed to the prior era of babies starting dialysis below 1 year of age, um, about 60% of them, um, uh, survived. And now in the red line here, these are kids less than 1 year, um, about 80% survived in this registry. So, over the last decades, I think we've, we've gotten better, um, as, uh, this, this, this has shown us. If you put these studies together, um, I wanna just kind of show you here on the right side that, um, some of these registries, again, that are, that are prior to, you know, the, the new era, uh, but they're looking at, you know, about 80% survival in these patients who make it at, um, uh, to the registries and end up, uh, looking at, you know, long-term 5 year survival. But I think it's important to recognize the limitations of these registries, uh, because I don't think they really tell the full story. Uh, many patients, uh, and parents are told that their fetus can't survive with kidney anomalies, and so they terminate their pregnancies. Uh, maybe babies are born with kidney anomalies, uh, aren't given a chance at life. They're born and they're, they're basically, um, told that they can't live, um, especially, uh, if their lungs don't work so well. Again, um, as I've showed you with those prior cases, I think that story is evolving. And, um, and I think as we're learning about how to do kidney support therapy, I will argue that many babies are not given the optimal care and support, uh, but that is going to change as, um, nephrology is getting better, and there's a, a big focus and emphasis on, uh, learning how to do, uh, dialysis for babies better. And, um, and then lastly, I'll mention that in these registries, um, many of the patients who are born and are trying to, to have, um, um, survival, um, don't make it to the registry. So you have to essentially leave the hospital to make it onto those registries. And so, um, again, something to consider as you kind of, uh, look and think about those registries. So clearly we need some, some newer registries that are gonna allow us to understand uh what this current era, uh, what their outcomes are. Um, should all babies with end-stage kidney disease be dialyzed? Um, I don't know. Uh, certainly, there's people that, that would argue back and forth, uh, of when and how. Uh, certainly, it deserves, uh, um, a major conversation with all the stakeholders, especially the families, to recognize what they're, what they're in for. Um, and best case scenario, they'll have, you know, 6 months or a year of, of really difficult hospitalization. Um, and, and therapies and dialysis and long-term, uh, the need for, for transplant. But once you've made a decision to, to support the baby, um, let's talk about what we can do to make, make the likelihood of a good outcome best. OK? So, once you've made a decision, don't look back. Let's make it work. And, and so, when we talk about, uh, kidney support therapy, um, Dialysis, renal replacement therapy, whatever you wanna call it, um, there's certain principles that are important for you to understand. There's two types of dialysis. One is through the blood, and one is through the peritoneal dialysis cavity. Um, and there's different sequences. So you can do it 24 hours a day, you could do it prolonged, which usually means 8 to 12 or 16 hours a day, and then intermittent hemodialysis, which is, you know, 3 to 4 hours a day, um, Generally performed in babies daily or every other day. Each of these has advantages and disadvantages, and the choices um of what to use are guided by the patient, the goals, and what you have available at your um at your institution. Um, I think of them as tools, um, and so if you have a, a, a nail that you need to push through a board, you could certainly do that with a paintbrush, but if you have a hammer, uh, pull out the hammer and, and accomplish the goals that you have in front of you that day, with the, with the options that seems to, uh, be less likely to lead to problems, and more likely to get you to accomplish your goals. And so what are the goals? What are we, what are we supposed to be doing when we take care of a patient with dialysis? Well, we have to, you know, be the homeostatic function because the kidneys aren't functioning. So we have to make sure that the electrolytes, the water, the uremic toxins are really kind of where we want them to be. Um, and we also have to make sure that we allow plenty of opportunity for provision of the things they need, the calories, the medications, the drugs, the blood products, uh, that they're gonna need, um, to, to, to do well. And what it shouldn't do is shouldn't cause problems, it shouldn't cause hemodynamic instability, it shouldn't cause bleeding, shouldn't mess up your vessels. So, ideally, you have, um, you provide a therapy that doesn't cause these problems. And probably as important is that, you know, your therapy can't freak people out, OK? If, if people are walking, you know, dialysis machine into a patient's room, And the mom starts crying and the parents, you know, and, and the, and the nurses are nervous, and the neonatologists are, don't understand what's going on, um, then, you know, that, that's, that's limiting our ability to really uh provide the best care. So, Let's talk a little bit about peritoneal dialysis. Peritoneal dialysis is great. Uh, we use it all the time for different situations. Um, most of the babies in the registries receive peritoneal dialysis. It's simpler, and it's really a goal that we need to get. You to go home because um most of the time, um, in the outpatient arena, peritoneal dialysis is much simpler to do than having incenter hemodialysis. Um, um, and so, generally, we have to get the kids to be around 6 kg before they can go home. And, and certainly in most of these kids, the goal is to have them on peritoneal dialysis, um, you know, uh, to, to be able to, to sustain life through, uh, through home peritoneal dialysis. But the problem is that ideally, um, we should not be using peritoneal dialysis for the first week or 3. after we place the catheter, we can, uh, but it's just less likely to work well. There's, there's more likelihood to be malfunctions or complications, leaking, infections. Uh, so ideally a peritoneal dialysis should be held for a couple of weeks, uh, for it to be healed before we use it. And it's not necessarily appropriate in all cases. Um, if you need to have very, very tight precision on fluid balance, where you're making changes from hour to hour, um, it's not as ideal as, um, as continuous renal replacement therapy with, through the blood. Um, certainly, it's not ideal when the PD is not working. If it's leaking, if it's infection, if it's malfunctioning, we could try to kind of, you know, work around those problems, but it's really not ideal. Um, and certainly, there's situations where you have an abdominal process, for example, the baby we had with the gastric perforation or if you have someone who's got, you know, uh, needs a colostomy, uh, where you can't really, uh, use peritoneal dialysis. Intermittent hemodialysis, I mentioned, um, is the most efficient approach, but it comes with certain problems. Uh, the hemodynamics can go off when the machine is initiated, and really, um, it's, it's great when you can accomplish everything you need to in 3 or 4 hours of time. Sometimes that's not possible in these kids, and so you may need 6 hours or 24 hours to really accomplish the goals in a steady, um, and, um, um, systematic, um, gentle way. So why not traditional CRT? This is something that we've been using for a long time, uh, but these machines that have traditionally been used, um, are too big. Um, I'm gonna talk about the HF 20, which is a new filter available in the United States. It's 60 mLs extra corporal volume. That is about half of what it used to be. So up until now, we had circuits that were double. But even this circuit, I just wanna walk you through kind of the thought process behind it. So, if you have a patient who's 3 kg and they, um, the blood volume is about 80 per kilo, that means a baby, a term baby will have about 240 mL of blood inside their body. And so if you're taking 60 mL out to get the machine started, that represents about 25% of their total blood volume to get the machine started. So, that's great, and we can do that, and we can do blood primes, and we can kinda make it kind of uh less likely to have hemodynamics instability. But if you have smaller and smaller babies, so if you have a 1.5 kg baby, you can see that that then represents about half of their blood volume. Um, and if you have patients who are sick, who are on, you know, pressors and have pulmonary hypoplasia and pulmonary hypertension, Um, little changes in these human dynamics can really tip them over. And so it's not ideal for these babies when they're sick and when they're small. To give you an idea of what this would look like if you did it for me, I weigh about 70 kg on a good day, which means I have about 5 L of blood in my body. So you're, you'd have really high blood flows. Um, and essentially, if you compare this 25%, you know, extra corporal volume, It's about 1250 mL. So imagine if to get me started on a, on a machine, you have to take 1.25 L of blood out of my body to get me going. You could, you could see how possibly I may not like that very much, especially if I'm critically ill in the ICU. So, back in 2013, we, um we used to have these conflicting conversations with our neonatologist because I was frustrated that they would call me uh when the patient was already very swollen, when the patient was already, you know, had a very significant problems, when they were, you know, really already started to be malnourished. Um, and so there was a frustration and I would come back and say, look, you know, you gotta call me sooner. And, and one of the doctors that I work with, uh, we'll call him Doctor Diaper today, um, you know, he basically pulled me aside and said, listen, we like you, but your machines don't work. They're a pain in the butt. Uh, my nurses are not very comfortable. My patients are crashing when you start the machines. Um, and it doesn't work so well. Um, they have all these complications. They call me at night all the time and I just don't like them. So The question that, that came to me was to say, well, what if we had a smaller circuit? Um, a clever person solves a problem, a problem, a wise person avoids it. So if we had a smaller circuit, maybe we can avoid all these issues that we're having, and, uh, and maybe that would change things. So, in theory, it would improve the hemodynamic stability. We would be a, uh, able to use smaller access, um, smaller catheters for these babies with that have smaller vessels, have less blood exposure. And essentially, potentially this could be a game changer. If it could decrease or change that risk benefit ratio, maybe they would call me sooner when I thought it was more appropriate. And so, we found this machine that was uh uh FDA approved for adults, for ultrafiltration. Um, it's small, it has an extra corporal volume of about 33 mLs. So it gets the uh 4 kilokedo down to about 10 10% extra corporal volume. So now we have this circuit that we, is, is small, and potentially would be useful. Um, it does not have the ability to do dialysis. But we came up with this idea to say, well, what if we do what we call replacement with CVH where we infuse some, some fluid through the circuit, um, and we do some Y connectors to kind of make it all kind of rigged up correctly, and do what, um, what we sometimes do, um, with continuous, um, renal replacement therapy, uh, by, by clearing with convection as opposed to dialysis. Well, it worked. And uh we have now done um um 91 babies in our NICU since 2013 with this therapy. Um, I will tell you that, um, if you look at this chart, um, this is back in 2003. We did very little dialysis in our NICUs, uh, with the, the, uh, Prismaflex, the machine that I showed you earlier. And, um, and you could see the number of patient days that we do. In our hospital over the last several years. Um, and, uh, we now do more days of CRT in our NICU than we do in our PICUU and cardiac ICU combined, partly because we're using the, this, this modality on these babies who have end-stage kidney failure. So, in 2008, we had several kids with end-stage kidney disease that were on circuit for, for months and months. Um, and so that's why you saw this, this big blip here. Um, this is the survival across our cir uh, our hospital, um, NICU, uh, both kidney, with patients who have acute kidney injury as well as those with end-stage kidney failure. So you could see that the mortality rates, um, um, are decreasing in our survivals, um, are getting better over time. You can see here that um very few times during our initiation of the therapy, we need to do anything to these babies. Uh, we don't need to give them blood, we don't need to give them volume, we don't need to give them calcium repressors, we don't need to make any adjustments. And the, and the 2% of the time that we've had these interventions needed during initiation, they were pretty mild, a little bit of calcium or a bolus of saline, uh, adjustments in their dopamine. And over here on the right, you could see that year over year, um, most of our circuits are lasting plenty long. And so the, the benchmark that we have is that our circuits should last for at least 60 hours, and you could see that, um, about 60% or 70% of years of our circuits last for, you know, 2.5 days or longer. We, uh, published our data, um, um, with our friends at Cincinnati Children's and Seattle Children's Hospital, um, and, um, it was a three-center retrospective cohort from 2012 to 2018, and, uh, and we describe our experience, um, mainly to point, point out that not all the babies survived the hospitalization, but most of them survived their initial, um, CRT procedure, and we had very little, um, Um, need for cardiorespiratory support at the time of initiation. So So now we're in a situation that we can look back on what we're supposed to be doing, and I could tell you with uh um confidence that we can do it. Um, we can make your electrolytes, sodium, potassium, phosphorus, whatever number you want it to be. Uh, we can clear as much or as little as you think is necessary. Um, and, uh, we can allow for provision of calories and anything else you need, because when they're on these circuits, you can give them 200 per kilo, 400 per kilo, and I'll take that off, uh, without having any, um, uh, problems with, uh, fluid balance. And perhaps more importantly, is that now we can do this without hemodynamic, uh, problems, without bleeding, without vessel damage, um, and people don't freak out. Everybody seems very comfortable in our institution to do it. Our nurses at the bedside are trained. In a simple um machine compared to some of our other things. And our neonatologists, you know, understand this therapy and they recognize that it's not such a big deal anymore. I'll tell you that there's another machine out there that has recently been FDA approved. Um, it's called the Carpodium. It was designed from the ground up to really be a machine for, for small children and babies. It's got all the bells and whistles, and, uh, and it's also a machine that, that institutions are starting to get, and, uh, and it's also gonna be kind of a game changer in how we take care of babies, uh, who need, uh, kidney support therapy. So our current approach is, number one is these babies gotta grow. If we can't grow them, then we're really just spinning our wheels. Um, we don't withhold nutrition to avoid dialysis. I think it's a really bad idea. Um, And as I mentioned, if you're on CRT you can give him as much fluid as you want, because we're, we're gonna be right there taking it off. And it's really about finding that balance. You're deciding what our goals are for fluid for that day, and we can, we can make adjustments in our machine to achieve the goals that we want. Um, so, the second is we start dialysis when the babies need it, so we don't wait until the baby is starting to be malnourished, or a fluid overloaded, or uremic before we start. We look at the baby and say, well, is the baby able to, to maintain homeostasis of fluid and electrolytes, and, um, and uremic toxins. Uh, if they can, wonderful. Uh, if they can't, if we can't get them big, if we can't give them nutrition, uh, we go ahead and start. Again, avoiding complications is not just about uh the technology, although it's super important, uh, but really it's also about educating our team, uh, developing the right processes and procedures to, um, to develop safety nets, because these patients are fragile and, um, and small changes can happen that could tip them over. Um, we've learned that, um, Preventing and treating pulmonary hypertension is very important in these patients. Um, so, the things that neonatologists know well about pulmonary hypertension, Um, need to happen in these patients, otherwise, we end up getting into, into problems and, and, uh, really can't get them off of ventilators and nitric oxide, etc. But if we can do that, um, as well as to get these kids' lungs bigger, uh, we, we can have success and get them off these therapies, and, uh, and get them off, um, uh, ventilator and oxygen support. Um, and then finally, you know, options are really good. Devices, uh, and these approaches that we have are complementary. Those babies that I mentioned to you at the start of the talk, um, all of them received CRT, intermittent hemo, peritoneal dialysis, and it's really about what makes sense for that patient at that particular moment, uh, to help them kind of get to where we want them to be. And lastly, um, having a surgical team and having the right catheter placed at the right time by the right person and the right vessel is essential, uh, for us to be able to do this work. This is a study that we recently published in Pediatric Journal of Pediatric Surgery. Uh, we'd like the 6 French power honed double lumen catheter that is, um, able to be cut to the desired length, um, so that we could put it in the, the perfect little window, um, where these patients need them to be. So, um, to put this all in context, then, um, again, it's hard to compare to other registries, uh, but, again, for the reasons that I mentioned, but I will just mention that, for example, in that USRDS database, there was 372 patients in the, in the entire United States over a 14-year period of time. Um, in those other studies, 5 countries, 264 patients, um, we're doing a lot more than that if you think about one state doing, um, in 5 years, doing 27, uh, patients. And so, we're doing, you know, a lot more patients than, than previously. Um, and these patients are much Thicker, uh, many times. Um, I'm presenting patients that needed, uh, CRT, uh, so the patients who ended up needing peritoneal dialysis aren't really, uh, these 27. These are really the 27 patients that, uh, were the most, um, dependent on dialysis, if you can, if you can, uh, state it that way. And, um, and again, uh, not all of the babies survived. These are, again, end-stage kidney failure patients at our institution over the last 5 years, and we have about a 50% survival rate. Um, and, and again, but these patients were super, super sick. I hope that our numbers are getting better over time. Certainly, in 2019 and 2020, um, those patients born then, um, had an 80% survival rate, but again, small numbers to, to know if it's a real trend. Um, I do wanna mention that if anybody is out there who wants to learn more about, uh, neonatal kidney support therapy, we have a course that we put on where we go through the machines, the, the, the different types of therapies, um, our approach to access, education, the prescription medications, nursing, uh, the PT and OT, uh, challenges that these patients have. Uh, so if anybody's interested, we have this course quarterly, um, and we spend a day and a half talking just about neonatal kidney support therapy. So, in summary, the decision to support a baby with dialysis, um, when they're dependent and have congenital kidney disease is not easy. And, um, and the care is not easy, uh, but I think the benefit rat ratio is changing. So, our conversations with families need to change in our approach to, um, registries and our approach To the outcomes that we're looking at when we do things like amniocentesis, I think need to change, um, because the, the evolution of kidney support therapy and neonates are, are going to continue to get better as more and more institutions, um, have these therapies available and develop programs to support their babies. Uh, kidney support therapy can be performed safely, safely in even really small and really sick babies, um, without Having them develop complications without freaking people out. Um, I tell folks, and I probably need to be careful how I say that, but if you bring me a really sick kid who's 1.2 kg, um, I feel pretty confident that our team can put him on circuit safely and could, um, again, support them, um, so that, uh, we can take care of him with all the other medical needs that we need. Um, it certainly takes time, education to build programs, to build collaborations. Um, you need dedicated families, um, really to give these babies a chance at life. And, um, I really thank you guys for your time, um, to, um, and, and for the opportunity to share our experiences, and, um, and I'm happy to answer any questions that you may have. David, this excellent talk. Um, I certainly enjoyed that a lot and learned a lot. Um, are there patients that you would not consider placing them on ACO? If, if they are, what are some of the criteria? Besides severe genetic abnormality, obviously. So that's a, a great question. I think that the The patients that we've had, we we didn't make the decision to put them on ECMO, um, in the sense that our neonatology and surgery colleagues, um, spoke to the families and they were placed on ECMO. So, so we weren't involved with that decision. We kind of were told later, hey, I have a patient on ECMO that we need your help with. Um, If it was me kind of providing people guidance, um, I think that Giving a, a, a child an opportunity on ECMO is potentially a reasonable thing to do if you have um a family who really understands what they're getting themselves into, recognizing that the likelihood of a, of a good outcome is not 100%, recognizing that even if they, um, even if they, the, the baby's gonna survive, it's gonna require multiple surgeries, multiple therapies, um, months and months in the hospital. Um, So, I think it, it, it's an individual conversation that, that you have to have with families. Um, I think the classic indications for ECMO or the contraindications, um, pre, really severe prematurity or, you know, um, has multiple congenital anomalies, I think, you know, still kind of, um, um, apply. Uh, but our institution is, is, you know, become confident that we can support these babies with Nutrition and fluid balance and electrolyte balance, and so they're, they're, they're offering it to their patients a little bit more. So what about bilateral renogenesis patient? Yeah, I think it's really It's a hard question. Um, I think it, it comes down to, do they have lungs that potentially could grow, and can you, as an institution, as a program, Provide them and grow them in context of them needing ECMO and needing, you know, such severe respiratory support for a while. Um, my job is to allow you to take care of the baby without concern for uremia, without concern for electrolyte problems, and without concern that you're gonna make them fluid overloaded. Um, and so, if you have a, a patient who, um, meets other criteria to, that you think that you could grow them by giving them nutrition, even without kidney function, um, then I think that, that at this point, it's It's possible to, to, to have a good outcome. Uh, we don't have enough data to be able to say, you know, the, the probabilities for different diseases, as you mentioned, or for, um, different severities of pulmonary hypo hypoplasia, hyper hypertension at, at birth. Um, but we're learning that what was possible, uh, five years ago is different than what's possible now for us. Thank you, David. That was great. I just, one quick thing, it's always great to hear the nutrition, um, idea be thrown out. We talked about this in our first, uh, session, but as a neonatologist, it's always a challenge when you're fluid restricting these patients so severely. Um, sometimes I think that contributes a little bit to the hypotension situation we can find ourselves in, but not being. Able to give these kids good nutrition is not giving them a good neurodevelopmental outcome, even if they survive to go home from the NICU. So I think the advent of a lot of these new therapies like modified aquaphoresis and like CP ADM is really gonna help us, even if they are survivors, improve ultimately their outcomes because we can give them better early nutrition. Yeah, I, I totally agree. I mean, the, the, we had a patient that was transferred from another institution. Yeah, the kid is, you know, a month old. By the time we got to him, he lost weight from birth. Uh, they were giving him, you know, very, very little nutrition because of those reasons. The PD catheter wasn't working and the kid was just starving to death and, and it wasn't surprising that they couldn't heal their PD catheter, that they were getting infections. Um, So, I think, you know, the approach of saying, OK, well, let's, let's do the things we know how to do well by giving them nutrition and supporting them. Um, let, let's, let's put the kidneys out of the picture. We can, we can do the job of the kidney well. Um, and so if we can do that, we, we, we work together with you and say, well, how can we get these kids big? Awesome. Thank you so much, Doctor Askenazi. I'm gonna move on to the next uh speaker.