Hello and welcome. I am Michael Morella, Managing Editor of Events at U.S. News & World Report. Today, we'll be exploring new frontiers in kidney care and sharing takeaways for healthcare leaders, clinicians, and patients about how to ensure the best possible outcomes for those facing chronic kidney disease, acute kidney injury, and other conditions. We have several distinguished leaders in nephrology and critical care who will share their insights. I want to thank BioPorto for their support of today's program. Before we turn to that discussion, just a couple of quick notes. We are recording video of today's session, and we'll be archiving that on usnews.com. Stay tuned for a follow-up email from our team. You can also find more details about today's program, speakers, as well as a range of other upcoming virtual events at usnews.com/events. Later on in the hour, we do hope to make some time for your questions. For those of you who are tuning in with us live, as you have questions, please type them into the Q&A feature in Zoom on your screen, and our moderator may give voice to those as time allows. Now, I'm very pleased to welcome our panel, whose full bios you can find on our event website. With us today are Dr. Ayse Akcan Arikan, pediatric intensivist and nephrologist who serves as the Medical Director of Critical Care Nephrology and Inpatient Dialysis at Texas Children's Hospital, and is an Associate Professor of Pediatrics at Baylor College of Medicine. Dr. Prasad Devarajan, Director of Nephrology and Hypertension at Cincinnati Children's Hospital Medical Center, and the Williams Endowed Chair and Professor of Pediatrics and Developmental Biology at the University of Cincinnati. Dr. Devarajan is also Senior Medical Director at BioPorto. Dr. Jay Koyner, a Professor of Medicine in the Section of Nephrology at the University of Chicago, also serves as the Medical Director of the Inpatient Dialysis Unit and Director of ICU Nephrology. Welcome to you all. Thank you so much for being with us today. Now I'll turn it over to my colleague, Shanley Chen, Senior Health Editor at U.S. News, to lead the conversation. Shanley. Thank you, Michael. I am very excited to have the opportunity to moderate this exciting discussion on kidney care with our esteemed panel of experts. Before we get into today's conversation, I'd like to have our experts tell us a little bit more about themselves, including your role at your institutions and the focus of your work and research. Dr. D, would you like to start us off? Sure. Thank you very much. First of all, I want to thank U.S. News & World Report for really recognizing the public health crisis related to both acute and chronic kidney disease, as well as the very exciting advances in the field that this panel will hopefully be talking about today. I want to thank the audience for tuning in. My name is Prasad Devarajan. I've been a basic and translational scientist investigating the biology of acute and chronic kidney disease for 40 years now. I've also been a clinical pediatric nephrologist for the past 35 years, and I've had the privilege, really, of orchestrating the care of fetuses, neonates, children, adolescents, and young adults with kidney problems at the individual, institutional, national, and global settings. I'm really delighted to be here with my two co-panelists. Thank you so much, Dr. Arikan. Thank you, Shanley. I will add to Prasad's comments and say it is incredibly exciting to have two pediatric nephrologists on this New Frontiers panel. It is an area that maybe does not receive as much spotlight as some of the other areas like pediatric oncology and cancer research, but certainly is going to emerge as a public health issue if we don't recognize the consequences of acute kidney injury and the growing population of CKD in patients. Thank you for including us. It is an incredible honor. Thank you to BioPorto as well. I am a pediatric nephrologist and intensivist. I was an intensivist first, t hen I trained as a pediatric nephrologist in an age where dual training was not very common. I'm the first in the States, but I also am one of the first in the world in pediatrics. This is quite common in the adult world. In pediatrics, I was one of the first. My career has started in clinical research with trying to diagnose and define acute kidney injury from the first standardized definitions predating KDIGO, and then has shifted into outcomes research in pediatric AKI, as well as all extracorporeal therapies related to critical care nephrology. I lead the Critical Care Nephrology Program at Texas Children's Hospital, and we probably are one of the biggest pediatric centers along with Cincinnati in terms of providing kidney care to children in the U.S. Thank you. Last but not least, Dr. Koyner. I'm Jay Koyner. I'm a nephrologist at the University of Chicago. I too want to thank U.S. News & World Report and BioPorto for having this and for recognizing what the adult nephrologists have known for a long time, that the pediatricians are leading the way around acute kidney injury. Maybe we're catching up, as we'll talk about later, from an adult perspective around CKD. I've been at the University of Chicago now for going on close to 25 years. I direct, as you heard, our hospital's inpatient dialysis unit and help build our ICU nephrology program because while Ayse has talked about not many opportunities for pediatric dual training people, it's not that there are a wealth of opportunities for adult folks. Here in the last three or four years, we've built a program to dual train folks in critical care nephrology. On top of that, I've been doing patient-oriented research around critical care nephrology, AKI, and how to better implement dialysis in patients who need it for the last 15- 20 years, including some collaborations with Prasad and others. I look forward to a fruitful discussion today. Thanks for having me. Thank you all so much. I'm very excited about this opportunity, like I mentioned. Let's go ahead and jump right in. In May, the World Health Organization issued a call to action for more comprehensive, coordinated kidney care around the globe, emphasizing the importance of kidney health and kidney care into broader, more holistic strategies for preventing and controlling non-communicable diseases. In general, can you explain what exactly the state of play in kidney care is today and how exactly does this rallying cry by the World Health Organization mean moving forward? OK, I'll try and put a start to this. It's very clear to all of us that the incidence of acute kidney injury and failure is skyrocketing globally and has now reached epidemic proportions. It's a public health crisis. It affects about 25% of hospitalized patients. It's an enormous problem. In my world, infants and children, about 30% of these cases are caused by congenital anomalies of the kidney and urinary tract. The kidney is the second most commonly affected organ in congenital diseases. We see a lot of this. In another 50% of the cases, the kidney is injured as part of another systemic illness, another serious condition, such as sepsis or multi-organ failure or nephrotoxin use. In both of these cases, we have had dramatic advances in neonatal and pediatric critical care. That has now allowed us to provide excellent supportive care for the kidneys and other organs, such that these patients are now surviving their critical illness. I could not have said this 10 years ago, maybe not even five years ago. However, these very, very sick children and young adults and adults who are surviving are living longer, but they are all invariably living with chronic problems and chronic conditions, especially chronic kidney disease, which extends into adulthood. There's no doubt now that acute kidney injury results in chronic kidney disease. The progression of chronic kidney disease itself is sort of punctuated by additional episodes of acute kidney injury. This has now resulted in a global epidemic of chronic kidney disease. One in three adults in the U.S. alone is at risk for chronic kidney disease. One in three adults are at risk, but only one in eight or one in 10 know that they are actually having chronic kidney disease. It is now suddenly our responsibility to recognize kidney injury and its risk factors early and prevent all those dismal consequences. We can effectively do that now by a combination of clinical phenotyping, predictive analysis, and early biomarkers that are now widely available and FDA cleared. That's the take-home message for me. It is now high time for widespread adoption and appropriate interventions. One more point I'd like to make holistically, we are now recognizing that all the scourges of chronic human disease in adults have their beginnings in childhood. This includes diabetes, heart disease, metabolic syndrome, hypertension. They all begin in childhood, and they all lead to chronic kidney disease in older children as well as adults. It is now my responsibility, our pediatric responsibility, to prevent that explosion of adult chronic kidney disease by early recognition and management of kidney disease and its risk factors during the pediatric years. I'll stop there. I'll just add on, I think that Prasad is right, whether you're talking about adults or kids. We are seeing more and more sick people. The things we can do to help save people are remarkable, whether you're talking about procedures and surgeries or chemo and immunotherapies. The other piece that is true that I think is part of the alarm is that we now have things that we can do to not just recognize, but to treat chronic kidney disease that we didn't have 15- 20 years ago. That 15- 20 years ago, when I was finishing training, it was, we're going to put you on an ACE inhibitor or an ARB. We're going to keep our fingers crossed, and we're going to maybe think about looking at your protein every once in a while. Now, on top of those RAS inhibitors, we've got SGLT2 agents, GLP s, and MRAs. Part of the alarm in my mind is not just, hey, there's a lot of it, but there's a lot of it, and we need to treat people for it. People need to know because there are not enough nephrologists in the world. You heard Prasad talk about one in three and only one in eight or one in 10 knowing about it. We don't have enough nephrologists, adult or pediatric, to care for all the people and to risk stratify them. Part of that alarm in my mind is letting primary care providers, letting other cardiologists, letting other people know, hey, this is an issue, and we're going to need your help because we finally have the first line of agents that we can to improve these outcomes. Whether you're talking about first-line biomarkers to find people who are at risk for injury in the hospital or the first round of some of these medications to treat CKD when that person shows up in my chronic kidney disease clinic after their AKI in the hospital. You don't always want to start people on some of those agents immediately in the hospital when they're recovering from AKI. I think it's both a call for, hey, we have these new tools to identify people, but also on the back end, we finally have tools. I'm just providing you with the information from an adult side about, I don't want to say garden variety CKD, but you start talking about some of the more exotic forms of CKD, IgA, polycystic kidney disease. There are more and more therapies for us to be treating those people with that are even sort of beyond the scope of what we're going to talk about today because there's so much CKD from hypertension, from diabetes, related to metabolic syndrome that you heard Prasad talk about. I would ramble, but I promised Ayse I would not talk for how long we do it. I can talk for the rest of the 60 minutes. Jay, you're absolutely correct. While Prasad was talking, I was thinking about highlighting this for our audience one more time. There are not enough nephrologists, but pediatric nephrology is in a staffing crisis. It is incredibly understaffed. It's a very difficult subspecialty. We don't have a lot of trainees who are interested in going into pediatric nephrology. Pediatrics, as you know, have not ever been appropriately compensated. Pediatric specialists are not really compensated at the level of our adult specialists, even though compensation overall is not where it should be in terms of compared to effort. However, we simply do not have the numbers in nephrology to be able to take care of these patients. It is in the population. The people who take care of the population, we need to rely on them. We need our pediatricians to understand that children who are recovering from AKI, even seemingly mild AKI, are coming back to their practice with decreased renal reserve and potentially other impacts on remote organs, which I hope we can talk about in terms of non-renal consequences of acute kidney injury. Also, our internists, our general practitioners, our family practitioners, if you actually don't look for kidney health markers by ordering the simple filtration tests and the newer biomarkers that are available to us, you're not really going to be able to diagnose this since it's a silent disease. The target for us is the subspecialists and the general practitioners, really, so that they can understand they're seeing this every day in their practice, both inpatient and outpatient. Absolutely. We definitely will get to more about that, about the need for interdisciplinary approaches and care coordination later on in our discussion today. Before we jump into that, the one thing that I did want to start us off with is something that you all had mentioned, the advances that are being made in the field. There have been tremendous strides already made in the field of kidney care, including advances in diagnostics, treatment, and research, particularly biomarkers, as all of you have mentioned. In fact, Dr. D, I understand you made the groundbreaking discovery of the NGAL biomarker for acute kidney injury, which laid the foundation for the first AKI biomarker test to receive FDA clearance for pediatric use. Talk to us more about the NGAL biomarker and what exactly this means for early intervention. Thank you. I'm going to summarize 25 years of work in two or three minutes. The AKI biomarker story really began about 25 years ago, when the nephrology community realized in the clinical setting that AKI is becoming reasonably common. AKI has serious consequences upon treatment if recognized late. The available diagnostic biomarkers at that time identified kidney dysfunction, but could not identify kidney damage early enough to benefit from a variety of preventive and treatment regimens that worked very, very well in the experimental setting in animal models, but none of them worked in humans. Why is that? We can get to that in a minute. Because we lacked those structural injury markers similar to troponins for myocardial infarction, we went fishing. We used all the possible genomics, proteomics, metabolomics, and by we, I mean the nephrology community as a whole, not just me. We found some targets. One of the targets we found was NGAL, which was by far the most upregulated gene in the kidney in a whole variety of acute kidney injury models in animals. Because of that, we also found that the NGAL gene encoded for a protein that is very, very rapidly translated and secreted into the urine and into the blood. That was our aha moment, our tipping point, saying, aha, maybe we can look for this marker in the urine or in the blood. Yes, that's 25 years of work, and that indeed is exactly what happened. In the meanwhile, we discovered that NGAL is a nephroprotective agent. It prevents damage to the tubule, and it prevents bacterial growth. It's a bacteriostatic nephroprotective part of our normal innate immune mechanism. There's a very strong biologic plausibility of why the kidney decides to upregulate NGAL more than anything else. Long story short, we created some ELISAs, and we were fortunate to partner with industry to take our assays and then put it onto standardized laboratory platforms that anybody in the world can use. That was a big breakthrough. I want to thank my industry partners for doing that. They also put together the study that allowed us to get the FDA clearance for this assay. Now we have a biomarker. There are other biomarkers available. You asked me about the NGAL story, and that's what it is. It is now available. You can put it on any standardized laboratory platform anywhere in the world. It gives you a return of result within 20 minutes with just a few drops of urine or blood. We've been using it routinely for seven years now in patients at clinical risk. We define that based on epidemiology and artificial intelligence and things like that that my two colleagues know much more about than I do. We cherry-pick our patients, and then we use this marker for predicting or excluding structural acute kidney injury in clinical settings. We use it for differentiating between functional and structural injury. We use it to predict need for dialysis. Very importantly, we now use it a lot in drug development. The FDA has cleared this marker and a few others as safety markers to be used in phase I clinical trials of medications that might have potential nephrotoxic potential. That is where we are with NGAL. It's an explosion in more than 2,000 publications. I can't keep up with this anyway. That's very exciting and seems to have huge implications for patient care and improving health outcomes for your pediatric patients. In terms of adult nephrology, what lessons can adult nephrology learn from the pediatric success in pushing that biomarker adoption forward? The FDA study that has obtained NGAL clearance up to the age of 21 has now been extended to the adult population. Dr. Koyner is one of the principal investigators of a current clinical trial that is aiming to show that it is equally effective in adults. Jay, I'll hand it over to you. I mean, as I sort of alluded, thanks, Prasad. As I alluded to, the idea is that just because something works in kids doesn't mean that it's going to work in adults. We have to check to make sure. I think the thing I want to piggyback on that Prasad was talking about is that I think we oftentimes focus on the power of a positive test, by which I mean the test identifies people who are at high risk for AKI so that you can rally the troops and figure out what you're going to do about that impending AKI. I think it's just as important to think about the negative tests. Having used other biomarkers that are available, those are just as useful, and in my hospital, almost more useful in the idea that if you were concerned that this patient has a risk for severe AKI and your reliable test is telling you no, there isn't any tubular damage, that for folks like us means that you can start rallying the troops for other things, like getting that patient out of the intensive care unit and/or de-escalating the care that that patient is receiving so they can leave the ICU faster so that there can be a quicker turnaround because we all live in a world where the minute someone leaves an ICU bed or a hospital bed, for that matter, there is someone else to fill it up. That throughput is a word I don't like to discuss, but is a very real phenomenon. We on the adult side want to piggyback off of what the pediatricians have learned. For sure, it's great to say it's not great when the NGAL is high, but it's great to be prepared in advance and be able to have those discussions about whether or not you want to prepare for things like dialysis or whatever the next steps may be for that particular patient. It's also super useful to think about the value of a negative test because you're going to have way more negative tests than you are positive tests. Just because we know that the rates of severe AKI are low, we just don't have the tools to figure out who is going to go, which patients with Stage 1 AKI, as an example, will go on to Stage 2 and to stage 3. That creatinine, urine output, BUN, whatever other marker that you are currently using in your hospital has already been shown repeatedly to be lousy at determining that in the supermajority of people. The test has sort of dual benefits. We focus on, well, if it's high, we have to then call the intensivist will call a nephrologist. If it's low, there's lots of things that the intensivists can do on their own to get that patient healthier faster and get them out of the hospital or the ICU faster. I hope I answered the question. Yes, you did. It seems like there are a lot of incredible advances that each of you are doing at your institutions in the field to really help those patient outcomes. One of the things, Dr. D, that you had mentioned too is this concept of artificial intelligence and the practice of artificial intelligence. Without a doubt, AI is rapidly transforming the healthcare industry, offering significant potential to improve patient care, streamline operations, and as you had mentioned, advance medical research. Dr. Arikan, you're actually an early adopter of incorporating large language models in a clinical context. Can you tell us a little bit more about that? Yeah, thanks, Shanley. I think it goes a little bit further than that for our interest in data-driven, interactive systems that can actually act as learning healthcare systems based on our own data. Yes, AI is now overtaken all of the titles in day-to-day news outlets, and you can't scroll down social media for seconds without coming onto an AI application. There are alarmists and there are supporters. I think that as physicians, we have no choice but to be early adopters. I guess it's not really early anymore, but it's part of our lives. We do need to learn how to exist with it. Before we actually established our large language model research program here, we developed an availability of the real-world data that we actually collect through clinical practice. You know, in critical care and in nephrology, when you use devices, patients have a lot of data points that are some generated by the patients through vital signs and other clinical and laboratory data, and some through the devices we use, such as the dialysis machines that accumulate and flow into the electronic medical record that has now become the standard for every institution. Those clinically available data are incredibly rich, and it's very difficult to make sense of them unless we actually empower some machine learning technology or at least large data data science approaches. Otherwise, we are limited to capturing data once a day, which does not really even begin to scratch the surface of the complexity of patients. Texas Children's Hospital does a lot of CRRT for a pediatric hospital. We do about 2,500 days of CRRT a year, which means that on any given day, there is between six to eight patients on CRRT, whether it's an infant CRRT or a pediatric CRRT. The data that is being collected through these patients through our device integration program since 2017 or so has been stored in our medical record as part of the patient's medical record so that we now have access to an actionable dashboard that is queryable at any real time to not only show me as the operational leader where patients are being taken care of, but also be able to look and answer some questions in real time, such as, are we doing the right dose delivery? Are we actually hitting our targets in terms of survival of our filters? This was only possible through really embracing data science as part of our usual clinical practice. Now, large language models, as Jay also has experience with, are very tricky because they are prone to fabrication and hallucination. It is very important that we actually have experts who understand the content, who interface with these engines, and know prompt engineering in order to be able to leverage them. We are developing a program to try to predict hypotension that happens in dialysis patients so that we can actually predict it before it happens so that we can safely dialyze patients, both intermittent dialysis and continuous dialysis. That is in a research sort of scope for now, and it hasn't really translated into clinical practice. Cybersecurity becomes an important issue whenever we talk about data science. There are certain obstacles and red tape that need to be negotiated by clinical operational program leaders in order to be able to make data available so that we capture the complexity of our patients adequately. Excellent. Thank you so much. It's very exciting to hear what's going on at Texas Children's and what exactly you're doing in the field using AI. Dr. D, is there anything you'd like to add? No, I think Dr. Koyner is also quite an expert in this field. I would love to hear from him. I don't know that I'm an expert. In the land of the blind, the one-eyed man is king. I don't fancy myself an expert in AI, but I've partnered with people who are. About eight years ago, I partnered with a gentleman by the name of Matt Sharpeck when he was here at the University of Chicago, and we created a gradient-boosted machine learning model to predict AKI. We subsequently, as Ayse said, realized that that model, and we implemented it, and we performed a study that we just wrapped up. We realized that just like any test, it's imperfect. We then revamped it and have implemented a natural language processing large language model that we are currently in the process of enrolling patients in. The model that we've published, which was in CJSN earlier this year, the Clinical Journal of the American Society of Nephrology, is able to identify patients at risk for Stage 2 AKI 48 hours before there's actually changes in creatinine clinically. We have undertaken a prospective observational study where we are identifying those high-risk patients, and then we are biobanking samples to measure NGAL, urine albumin, and other biomarkers in their blood and their urine. I know that this is sponsored by BioPorto, but I've said this to the BioPorto people. I don't think that AKI is going to be like the Lord of the Rings, where there's going to be one ring or one test to rule them all. You're going to have to be able to understand that not all AKI is the same just because it's defined traditionally by a change in creatinine or urine output. There may be strengths of some biomarkers or some risk scores in the setting of sepsis or cardiac surgery or nephrotoxic-associated AKI. We're trying to unravel some of that. We know that our risk score is not perfect, that it still suffers from a positive predictive value of somewhere, depending on the cutoff you want to use, of 20%- 30%, which means that one in five or one in three people are going to have the outcome that we want. You don't want to be doing a whole bunch of, in quotes, unnecessary stuff on those two in three or four in five patients who are not going to have that. The hope is that combining the AI-generated natural language processing risk score with clinical biomarkers will then bring it down to better odds for your patient that one in two or even less than one in two of those patients are going to be the ones that you need to rally the troops for. We're in the process of doing that. We've enrolled over 150 patients here, close to 100 at the University of Wisconsin, and we're targeting over 400. I would hope by the end of the next calendar year, we will be done in publishing the results of that study. It's an exciting time, right? I think Ayse is right that if you're not embracing it, and even if you're embracing it now, you are kind of late to the game. This is where things are going, right? We all are using this to figure out what to watch or what to stream on TV already, or perhaps even what to buy your partner for their birthday or anniversary, whether you realize it or not, that those are things that are already happening in your life if you're on social media. I think that people's health is way more important than those other things that I was talking about. Using the tools and using them right and treating them the same way I said before, making sure that the test is doing what it's supposed to do. Just because it worked as you built it doesn't mean that as you implement it clinically, where there are things changing on a minute-to-minute basis, doesn't mean that it's going to hold up the same way. You have to figure out all of those things. Healthy skepticism is a sort of a reasonable way to think about it. Yeah, I'll just add to something Jay said because I do feel strongly about this. It's very easy to fall into this sort of hubris of, oh, anyone can do research in this area. Unless you actually have content experts like Jay, who are looking at the results and saying, these don't make sense, we will be led down the wrong path very easily using these methodologies that not all of us, I'm not a machine learning expert by any means. I just use people who are machine learning experts, sort of like Jay does. We have an obligation to try to understand what they're saying so that we are understanding whether they're actually performing appropriately or not. Otherwise, it would be garbage in, garbage out, just like with standard statistical analysis of frequentist results of clinical trials. We are hopeful that we are going to be able to leverage more of the, we're sitting on a lot of very rich data, clinical rich data that we don't have access to. These are tools for us to actually try to delve into it a little bit better so that we can understand which patient to treat where. AKI is such a heterogeneous syndrome. There are tons of different patients. Forget about the same patient with the same mechanism responding to treatments differently. Even when you use NGAL or cystatin C, which is another filtration marker, and you diagnose a patient with Stage 3 AKI, the etiology of that Stage 3 AKI might be 10 different things in my ICU. We are trying to understand patients a little bit better so that we actually can treat them the way they need to be treated. Those are all excellent points. As you had mentioned, it's very, very important that we understand as well as we're using AI so that we can use it responsibly. All of this is very exciting, whether it's AI or NGAL. On the other side of the coin are the challenges to these innovations and advances. For example, innovations that came out of the pediatric space, like CARPEDIEM, the infant pediatric device that helps support small babies born with severe kidney disease, have been game changers, as I understand, Dr. Arikan, you had mentioned before, in terms of care. Dr. D, you had mentioned that pediatric patients are living longer, but living with chronic problems. Dr. D, Dr. Arikan, as pediatric nephrologists, you see this a lot at your institutions. What are the ripple effects of increased survival in infants with severe kidney disease on long-term CKD care and system resources? I'd like to start by saying it's a two-way street. We learn from our adult nephrology colleagues every day, all of the time, just like they hopefully learn from us. The CARPEDIEM that you mentioned is actually a modified RRT machine that was initially designed for adults. It went the other way. Just to point out that it's a two-way street. Having said that, yes, it's very, very clear that these children and young adults that were dying five years ago are now surviving and are becoming an increasing burden, if you will, basically a healthcare crisis for both us and for the adult nephrologists to whom we transition our patients when they magically hit the age of 18 or 21 or 25, whatever it is. That has become challenging for the adult nephrologists because in many cases, they never saw these cases. They never saw patients with severe genetic disorders or severe clinical anomalies of the kidney and urinary tract survive their childhood and teenage and then suddenly become a burden for the adult nephrologists. It's a challenge, and we have to figure out how best to transition these patients. One of the ways that we've tried to do it and others have tried to do it is to train nephrologists both in pediatrics and adults, dual-trained people. They have been very valuable in terms of enabling this clinical transition. I think I'm going to add to what Prasad said and emphasize that we actually probably had a bigger epidemic than we realized, more so than the congenital abnormalities of kidney and the urinary tract that was above the surface of the iceberg. There are a lot of premature babies who survive, who had decreased nephron endowment, who are at risk for CKD even when they don't suffer any acute kidney injury. As a sign of how well adult and pediatric nephrology, at least in the world of critical care nephrology, specialists work together, I know for a fact that many of my adult nephrology colleagues, when they see patients with early CKD, they will ask if they were born premature as a baby. It's a new thing that adult nephrologists are learning from pediatric nephrologists, just like pediatric nephrologists have always been learning from adults and extrapolating. The CARPEDIEM machine, which actually was, as Prasad is right, of course, was invented by an adult nephrologist who was a good friend of ours, who was very interested in neonatal nephrology and was frustrated because of the lack of machines that were purpose-made, right-sized for the small infants that we take care of. One of the things that pediatricians always have to deal with, which comes naturally to us, is that our patients go from 500 g to 120 kg at 21, 24 years of age. All of the technology that we used until CARPEDIEM became available in the U.S. in dialysis of patients in the acute care setting were adaptive uses of the adult platforms. The standard Prismaflex, PrisMax machines that we use, and the similar other machines that are available in CRRT, many of them are labeled for not use less than 20 kg because they're not precise enough to be able to actually do safe fluid removal for patients. CARPEDIEM was a purpose-built neonatal infant machine. In our hands, for us, for Texas Children's Hospital and many centers like us, it has changed the topography of neonatal end-stage renal disease. We used to wait for babies who are born with abnormalities of the kidneys or who suffer AKI and lose kidney function for them to be big enough to put a peritoneal dialysis catheter so that we can actually support them with dialysis and grow them appropriately until we bridge to transplantation. Some never made it. Some were just too small, too sick, too fluid overloaded, too uremic, too catabolic for us to be able to actually have a successful peritoneal dialysis program established. CARPEDIEM has changed the narrative. We are now able to dialyze patients as small as 1.5 kg, 1.8 kg. In the absence of dedicated appropriate-sized hemodialysis catheters in the U.S., we use other lines that are made for infusion and jerry-rig them to use for dialysis. We have bridged many patients, successfully grown them on CARPEDIEM, and bridged them to transplantation. The activity and the number of patients that we're taking care of in many of the pediatric centers around the country is just going up. It's a direct trajectory. As kidney transplants don't last for a lifetime, when the need for a second transplantation arrives, very frequently, these patients are at the end of their stay with us. They're getting ready to transition to adult care. Just like Prasad mentioned, transition from pediatric services to adult services has become even more important as a ripple effect of what's happening with the neonates that are now surviving in greater numbers than before. Wonderful. I absolutely want to talk more about that transition from childhood care to adulthood care. Dr. Koyner, I wanted to throw this to you just to see what other challenges you're seeing, whether that be to funding cuts in research, care coordination complexity, or even access to care. Is there anything in particular that you find pressing in terms of challenges and concerns? I think we see some of the same. I think we're losing you, Dr. Koyner. I think we've lost your audio. Can you hear me? Mm-hmm. Hello? There we go. All right. I think that we see, sorry about that. I think we see some of the same phenomena. You can talk about kids with congenital disease, but the same thing is true in adults, which I mean whether you have heart disease or cancer. In my post-AKI clinic, I see people who have gone for two stem cell transplants and have now survived a CAR-T treatment for their leukemia and lymphoma. One of the biggest issues is that, as I said before, we have new treatments for people who have CKD that we didn't have years before. Not everyone has access to those treatments. Medications like SGLT2 inhibitors or MRAs or GLP-1 s are oftentimes expensive because some of them are relatively new. Some of the indications haven't necessarily made their way to the insurance companies in terms of the idea that people who have CKD and have proteinuria, whether it is from diabetes or some of the more exotic kidney diseases, will benefit from those medications. Working here on the south side of Chicago, I know that there are a large number of patients who do not have access to that medication or that when they go to pick up their SGLT2 inhibitor, the Jardiance, Farxiga, Invokana of the world, they're told that will be $500 they need per month. They'll need to decide whether or not they can get that medicine or they can do all the other things they can do with that. From my perspective, one of the things I want to highlight is that we at the University of Chicago have built a program around this idea where some of those medications, ACEs and ARBs, SGLT2s, MRAs, we have allowed, and the hospital here and the university deserves credit. We've put them on what we call the $5 med list, where if you have an approved indication for it, which gets verified not by your doctor, but by someone else, you have access to that medicine. When we talk about people living longer with kidney disease, that phenomenon is going to continue to happen, whether we're talking about kids or adults. Having quadruple therapy, SGLT2, MRAs, RAS, GLP s, is going to keep more people going for longer. We're going to wind up having those people, unfortunately, will have CKD and more AKI, but they need access to that medicine. I think that that's a huge problem. Problems like that have always existed on the south side of Chicago, where we serve an underserved, predominantly African-American population. They exist everywhere in the world at this point in time. Everyone understands that everything costs a little bit more, and whether you're talking about eggs or your medicine, people are making difficult choices. That's really problematic. We go from a situation where we had nothing to treat people, and now I've got options for them, but then they don't have access to that option. It can be heartbreaking. At least here, and I would hope one of the reasons that I'm doing this is so that other people can hear it and they can maybe reach out and approach their own hospital to make sure people have the care that they deserve, because we know that that's what they need. We know that that's best for you, whether you live in Houston, whether you live in Cincinnati, or whether you live in Chicago, or anywhere around the world. I just realized I listed a whole bunch of places in the center of the country, but East Coast, South Coast, wherever, right? We should all have access to these things. The same thing is true internationally, right? There are other places where access to these medicines is a non-issue. If you have the indication, you get the medication. It's ironic that I'm saying this because, as I think about it, the only place in the American health care system where that is probably true is dialysis, where we've had a one-payer system. If you need dialysis care, you've always had access to it in the United States. Now we have these things that we can use to avoid putting people on dialysis, and we're seeing hurdles being put up, whether by administration, whether by insurance companies, whether by pharmaceutical companies, to sort of prevent that from happening. We know that patients do better in order off dialysis, with a transplant, and then on dialysis. Dialysis should be our last resort for these people. I'm sorry. You hear the passion in my voice here. I'm going to take a breather and let you ask another question. No, we love the passion. We love to hear it. Absolutely. Thank you so much, Dr. Koyner. I've heard all of you mention very briefly the importance of coordinating care. Let's talk about care coordination, which is especially important in this area of kidney care, which involves an interdisciplinary team of health care professionals, as you all had mentioned, working together to manage kidney diseases and improve patient outcomes. Any insights or best practices on how to best coordinate care across specialists, settings, et cetera? That's a tough question, Shanley. It's very tough. On the one hand, nephrologists, I think, are in a little bit better place in terms of pediatric subspecialists in pediatrics. I don't know if Prasad will agree to this. Because we have CMS coverage with Medicare and Medicaid, and there are certain CMS-required interdisciplinary, multidisciplinary members, such as dieticians, pharmacists, etc., that need to be available to our patients for our ESRD and dialysis program, we understand that format is an incredibly beneficial patient-centered care program, as opposed to fragmented interdisciplinary support only at a fraction of the time that might be needed. Having a team that actually knows and knows each other and knows the patients works really well. Unfortunately, resource limitations are everywhere. One of the things that we are going to suffer significantly from in Texas, although I live in an incredibly affluent city, I live in Texas. Texas children mostly are on Medicaid. We're going to have a huge cut in our coverage of especially at-risk children. Some of these patients are not going to be able to come to ivory towers like us in order to be able to reach their care. Rural services are at very much risk. One of the things that happens when pediatric hospitals, maybe hospitals in general, but definitely when pediatric hospitals are at risk in terms of decreased funds due to lower availability, whether it's from the payer limitations or whether it's from other budget cuts and the rising cost of doing health care, such as cybersecurity threats, etc., the ones that are sacrificed most frequently are the non-revenue-generating clinicians, such as dieticians, pharmacists, social workers, school specialists, quality of life specialists, etc. It is a very rough battle for us, an uphill battle in order to try to retain the non-medical group or non-physician, non-practitioner group that needs to take care of these patients as part of the clinical care team so that we can appropriately do what we need to do to take care of all the patients in the hospital and as outpatient. It's a challenge for us. It is a challenge for us. That is within a specialty. If you talk about subspecialties or among different specialties, then that becomes even more of a challenge. I don't really think that I have a good answer for that. That's where, on the one hand, nephrology gives you an appreciation that you need to have this interdisciplinary team. On the other hand, you also don't, if you don't have the resources to be able to build it in other areas, there is not much you can do in terms of affecting change other than bringing it to people's attention, at least in my experience. Absolutely. That makes perfect sense. Dr. D, Dr. Koyner, is there anything else you'd like to add? I would sort of echo some of what Ayse said. I think that it very much depends on the situation that you're talking about, right? The nephrologist is always going to advocate, and I've always thought of nephrology as like a 300 or 400-level course in internal medicine, the same way that oncology is. If you're talking about on the inpatient side, for sure, embedding the nephrologist in the ICU or embedding them into ward rounds makes sense. If you're talking about on the outpatient side, there it's very different. At a place like, I think, at most hospitals, not even at a place like the University of Chicago, there are lots of resources in, say, cancer care, right? That's because in the 1980s, the oncologists did a fantastic job of advertising that cancer is this horrible thing, which it is, and kills people. I'm here to say kidney disease is a horrible thing and now kills almost more people than cancer does. If you get a diagnosis of kidney disease, depending on the type of cancer you're talking about, you're more likely to die from that kidney disease than you are from that cancer. There are lots of resources so that when I am talking about a cancer patient who has kidney disease, I can leverage the resources that oncology has, different than if I'm talking to the endocrinologist or the primary care doctor. I echo all of what Ayse said about some of our other providers on the team, that they're harder to marshal in primary care than they are, say, in oncology. I hope that some of what we're doing today is going to change that, the idea that we've known for decades on the adult side that if you talk about Framingham or MESA or many of these community-based epidemiology studies, what your kidney function is determines your cardiovascular morbidity and mortality better than what your cholesterol does, better than what your CRP does, and that it's been ignored. Maybe that's because as nephrologists, we've not been paying attention to it. We haven't screamed it from the mountaintops, or we haven't had opportunities like this to say it. We all know it's true. The other providers know it's true that if you've got kidney disease, that's a bad thing to have on top of whatever other problems you have. Marshaling the resources for that becomes super important. We're beginning to see some of that change. That's also because we now have things that we can do. That sort of learned apathy is maybe disappearing. There is still lots of work to do and lots of work to be done in terms of improving the care of those people. Just as we've alluded to, if we do what we're supposed to do and take care of those people and prevent someone from having Stage 3 AKI and only getting them to have Stage 2 AKI, who knows how many years on the back end that is going to save them. In those years, they are at greater risk for developing AKI. We are going to need the tools and the resources to take care of those people and rinse and repeat and rinse and repeat and rinse and repeat. Absolutely. The other thing that I've heard all of you mention before too is that transition from childhood to adult care and coordinating care during that journey. I'd like to ask you, what are you seeing and learning here? What are some of the best practices and approaches to help patients throughout that journey from childhood to adulthood in kidney care? Yeah, I can start. It's relatively new because we didn't have to deal with this even 10 years ago. Now, with all of these children getting very good intensive care, surviving their primary illness, and ending up with chronic problems, including chronic kidney disease, that has suddenly become a very large burden to society. We are learning how to deal with this and how best to transition these patients as they grow out of their age, where we deal with them, to our colleagues in adult nephrology. We have some strategies that have worked. Like I said, one of them is the combined med- beach training. For example, when one of my patients who I've taken care of for 20 years then goes to an adult nephrologist, I go to the clinic with them. I'm there when the patient sees the adult nephrologist just to hold their hands and make them comfortable that, hey, OK, this is going to be fine because there is a lot of fear, a lot of trepidation when that transition occurs. We have to make our patients and their families comfortable with it. Our adult colleagues are very smart, very capable, but they haven't been seeing this patient for 25 years or 20 years. There is a new relationship that has to be built. What we try to do is start that process, not at the age of 21 or 25, but at the age of 18 or 19. Start the process early enough so that there is a smooth transition. That has worked quite well for many of our chronic kidney disease patients and, in fact, very well for our transplant patients. What's really important, Shanley, as Prasad said, is that the smooth transition involves a pediatrician group. We have a transition clinic that we enroll patients in because this is obvious to us as pediatric nephrologists or pediatricians, but it comes as a surprise to our patients. We are used to talking to the family. We don't only talk to the patient. We are talking to the family as they're growing in our care. The moment they actually cross the threshold of the adult nephrology clinic, the patient themselves become the responsible person. They're signing consents, making decisions, being talked to, answering questions, and they're expected to have responsibility. That learning process, we found, takes a little bit of time. One of my colleagues here runs a transitional clinic with our adult medicine specialists, adult nephrology specialists. They see patients together for a while before they transition to adult services fully. We've found that this works really well. It's like a training program, like a little boot camp. We've gotten great feedback from the patients who have attended it. The ability to be able to actually smoothly transition increases exponentially when you're doing real-time handover. Wonderful. Thank you. Dr. Koyner, is there anything else you'd like to add to that? I would echo we don't have a formal transitions clinic here, but for sure, I have gone to pediatric clinics. If someone is 17 years old and they're dealing with a new diagnosis, rather than starting them for one year or for two years with a pediatrician, we'll start them with adult folks. I want to highlight what Ayse had said, that it's not just one doctor-patient relationship. Just like on the adult side, where you sometimes are treating the patient, but then dealing with the spouse or the son or the daughter, it's the same that you need to know what the home life is for that patient who's transitioning, whether it's mom or dad or grandma or grandpa or older brother or older sister. Who's the one that's going to get them to and from their appointments? Who's the one that's going to make sure that they're taking their blood pressure meds or they're taking the medicines that you want to start? The sooner you can do it, the better, because the piece that we haven't said is that kidney disease, for the most part, is a silent disease. It's a laboratory disease. People feel the same, right? Or maybe they feel lousy, but they don't feel that much more lousy because now they have kidney disease. Sometimes they do. It takes building that trust with the patient and with their family to say, this is an issue. This is our path. This is where I think we're going. We may have to zig or zag a little bit. It takes sort of a human touch. It's not something that can easily be explained unless people are spending time looking at their labs. Not everyone is doing that. I'm going to stop rambling. No, that's a very good point. Speaking of patients and patient families, as we head towards the tail end of our discussion today, I wanted to wrap up with one more question. Any take-home messages for patients, the parents, and the families about what to consider or be mindful of when navigating kidney conditions and diseases? In fact, we actually have an audience member with us today who has shared, "I have had type 1 insulin-dependent diabetes for nearly 60 years. In the last two years, I have been diagnosed with CKD Stage 3." What would you share with her or others in similar situations? I can start with that. Difficult, especially if you're asking for a very short answer. Really, it's all about awareness. We have to make the community and the patients and their families aware of this massive epidemic that we're all facing. It starts there with the patients and their families. We have to rally around the team, the political leaders, the hospital systems, pharma, regulatory agencies, decision makers in the health care industry, politicians, and even foundations like ASN, ASP, and NKR. We all have to rally together and stop the nihilism, stop this, become optimistic, and become new adopters and new adapters and stop being abandoners. That really is my message to the patients. It starts with the patients and the families, but the whole team has to rally together. The time is now. Otherwise, we're all going to live to regret it. That's a wonderful message. Dr. Koyner, Dr. Arikan? I'm going to say it might take advocating on your sons, on your daughters, on your behalf to be able to get some labs checked until we actually can get everyone on board to what Jay said. This kidney health assessment is not complete without blood work and urine work. It's not a physical exam. It's not a chest X-ray. It requires blood work. Ideally, it also requires a urine test. If there is concern because of past urinary tract infections, stay in the hospital, somebody stays in the ICU, there have been nephrology visits in the past in the ICU, or repeated stone disease, for example, and somebody is not completing the kidney health assessment in a usual health check, yearly check, that's incomplete. Sometimes it falls on our families. Sometimes it falls on our patients to actually advocate for themselves and to ask for these markers. One of the things that is very important for us is a filtration marker, a creatinine or a cystatin C in a usual state of health so that we know what the kidneys are doing in health so that we can decide how badly they're injured in disease. We want everyone to actually have urine analysis and a creatinine and a cystatin C check during a health care visit. Thanks. Spot on, Ayse, right? I tell my patients the same thing, that if whether you've had type 1 diabetes for two years or 20 years or 40 years, you've grown accustomed to the idea that you need to be checking not just your daily blood sugars, but then also your A1C every three months. The numbers that Ayse is talking about, I will add the urine albumin to creatinine ratio on top of it, should be part of the things that you're thinking about, right? Maybe not during those first year or two, but in the long term, that's what someone who's got 15, 10, 15, 5 years of diabetes, they should be thinking, when I get my A1C, I need to be thinking about, do I have protein? What's my creatinine? What's my cystatin C? What's my GFR as a marker of filtration? Then begin to think about if they have problems with blood pressure, think about their blood pressure the same way they've thought about their blood sugar. Know what the targets are, recognizing that depending on who you are, for good or for bad, 80-year-olds in my world have different targets than 30-year-olds. Knowing what your doctor says your target is, whether that doctor is a nephrologist or you don't have access to them because of the shortages we've talked to, primary care doctors, be they internists, family medicine doctors, whomever it is, sometimes it's the endocrinologists. They all know the data. They know that this is what they need to do. If you're not getting the care that you think you need, you know, advocate for yourself. Sometimes it's not so easy, but that's, you know, do it because no one else is doing it for you. Absolutely. Absolutely. Advocating for yourself. Very, very critical information. Thank you all so much for sharing your insights. We might have a few more minutes for one or two questions from the audience. In fact, we have a few. The first one that I would like to ask you is from one of our audience members. AKI is not a topic that has been taught for very long. How can practitioners update their knowledge of AKI and CKD topics, as well as KDIGO updates? Wow. I mean, I think that there are lots of ways. I think we, as a nephrology critical care community, have tried to do a good job of spreading the word. I know I've been to non-nephrology meetings with Ayse and Prasad, whether they be cardiology or ICU meetings. I think, yes, I remember being in med school 25 years ago, and AKI was sort of this thing that was taught but wasn't taught. If they get better, they get better. If they don't, they don't. Now we actually have tools to do it. Engaging with your nephrologist, who should be invested in caring for and optimizing the care for patients who have AKI. Here, I put a plug in. I'm going to be in Houston with Ayse in a few weeks at the ASN meeting, ASN, the NKF, the CRRT meeting, the ERA meetings in Europe, if you're watching across the pond. They all have tracks that are dedicated to improving the care of patients in AKI. Yes, even in places like the SCCM and CHEST and ATS, there are little spots here or there for hours over the course of three, four days where they talk about how to care for patients who have AKI. The pulmonary folks and the cardiology folks, you know, it's not the focus, but they know how important it is. More and more, you're seeing those topics addressed in other places. Same thing is probably true. I haven't been to too many endo meetings because I'm more in the ICU than outpatient CKD focused. We're getting the word out. I would hope that three, four years from now that that question doesn't exist because people will know more. Be proactive. Just like I told the patients, advocate for yourself. If you're a provider, go seek out that education. Have a conversation with your nephrologist. Nephrologists like to talk about kidneys, maybe even a little bit too much. Excellent. Thank you so much. It looks like we are a little bit over time, but I want to thank you all for participating and for sharing your insights. That concludes our session for today. My sincere thanks to our panelists for their valuable time and insights, as well as to our audience for joining this discussion. Just a little reminder, a recording of today's event will be shared in the coming days. Please don't forget to visit usnews.com/events for information on upcoming events. You can also find a wealth of content, rankings, and other insights from our health team at usnews.com/health. Thank you again for joining us. I'll see you all next time. Thank you. Thank you. Thank you.