Selected Podcast

HF20 Filter Set for CRRT in Low Weight Patients

Dr. Stuart Goldstein discusses the HF20™ study as well as its endpoints and the clinical gaps the study addresses.
HF20 Filter Set for CRRT in Low Weight Patients
Featuring:
Stuart Goldstein, MD
Stuart Goldstein, MD, is Professor of Pediatrics and Director, Center for Acute Care Nephrology at Cincinnati Children's Hospital Medical Center. He received his medical degree from Columbia University and completed both clinical and research fellowships in pediatric nephrology at the Children's Hospital in Boston, Massachusetts. Dr Goldstein is Founder and Principal Investigator for the Prospective Pediatric Acute Kidney Injury Research Group, and has evaluated novel urinary AKI biomarkers in the pediatric critical care setting. He was one of two pediatric work group members for the KDIGI International AKI Guideline Work Group and has served on the KDOQI Hemodialysis Adequacy, Vascular Access and Pediatric Nutrition Guideline Work Groups. He has written over 300 journal articles, served as editor of two textbooks, and contributed book chapters to numerous texts including, Critical Care Nephrology, Evidence-Based Nephrology, Handbook of Dialysis Therapy, Management of Acute Kidney Problems, Pediatric Critical Care, Pediatric Nephrology, and Pediatric Nephrology in the ICU.
Transcription:

This podcast is sponsored by Baxter Healthcare Corporation. When you choose Baxter for your CRRT program, you're not only choosing true patient-focused treatment with industry-leading CRRT technology, you're also selecting a partner dedicated to optimizing your clinical success in treating patients with acute kidney injury.

Our commitment to you starts with the program individualized to your facility's needs and provides complete support every step of the way. For more information, visit us at www.renalacute.com.

Baxter Healthcare Corporation has provided funding for this podcast, but all content was developed independently by the presenter. Therefore, the views expressed on the podcast are those of the speaker and should not be attributed to Baxter Healthcare Corporation.

For prescription use only. For the safe and proper use of this product, please refer to the operator's manual.

Dr Pam Peeke: Hello and welcome to the Society of Critical Care Medicine's iCritical Care podcast. I'm Dr. Pam Peeke, your host. Today, we're going to be talking about continuous renal replacement therapy in children.

I'm joined by Dr. Stuart Goldstein, Professor of Pediatrics and Director of the Center for Acute Care Nephrology at Cincinnati Children's Hospital Medical Center. Dr. Goldstein received his medical degree from Columbia University and completed both clinical and research fellowships in pediatric nephrology at the Children's Hospital in Boston, Massachusetts. He's founder and principal investigator for the Prospective Pediatric Acute Kidney Injury Research Group and has evaluated novel urinary AKI biomarkers in the pediatric critical care setting. He's written over 300 journal articles and served as editor of two textbooks and has contributed multiple book chapters. Dr. Goldstein, welcome to the podcast.

Dr Stuart Goldstein: Thank you so much, Dr. Peeke.

Dr Pam Peeke: So before we begin, do you have any disclosures to report?

Dr Stuart Goldstein: Yes. I served as a consultant for Baxter Healthcare and also receive grant support from Baxter Healthcare and Baxter is the maker of the HF20 CRRT filter.

Dr Pam Peeke: Excellent. Thank you so much. Dr. Goldstein, in your estimation, why is this podcast needed?

Dr Stuart Goldstein: I think what's really important, Dr. Peeke, is that for many, many years, there have not been devices that are specific for the most critically ill children who require continuous dialysis or continuous renal replacement therapy. And so pediatricians and intensive care units, both intensivists and nephrologists, have had to use devices off-label, and has had to adapt the use of those devices in kids.

We know from work that we and others have performed that acute kidney injury is independently associated with mortality for critically ill infants, neonates, and larger children. And part of what we found in the last decade or so is that kids who were under 10 or 20 kilos in weight have increased mortality if they develop AKI and requires CRRT.

So why I believe this podcast is important is that the HF20 filter addresses an important gap in the care of children. It is really aimed at supporting children who are 8 to 20 kilos in size, where there has not been another device available for them. This device has been available in Europe for many years and is currently available in the United States under an emergency use authorization for COVID. So that's why I think this is an important podcast to let people know about this device.

Dr Pam Peeke: What are the knowledge gaps? What's going on out there in the real world, in ICU, as it really pertains to children who really need this type of therapy?

Dr Stuart Goldstein: You know, Dr. Peeke, I think it's not so much of a knowledge gap as that it's really a financial gap. These are orphan diseases in terms of the way the FDA perceives it and the way that we think about it. As opposed to adult medicine, there are fewer than 4,000 to 8,000 children in the United States annually who require CRRT. And then when you slice that pie even smaller, for kids under 20 kilos, becomes less than about 30% of those patients. And so there has not been really the financial return on investment to think about developing devices that are specific for this incredibly vulnerable population.

Fortunately though, I can say over the last 5 to 10 years, including the HF20, there has now been a push to provide devices that are specific for smaller children. And that has a huge impact on them because with larger devices, we often have to prime the circuit with blood to allow and promote hemodynamic stability for smaller patients. If you use a large adult filter and you don't prime that filter with blood, you can cause anemia and hemodynamic instability for the patient.

So what's the big deal about blood priming? The big deal is that we now start to sensitize some patients who are not going to recover their kidney function and therefore decrease the donor pool for available kidney transplant donors for these patients. Therefore, having devices that are specifically made for smaller kids allows us to avoid blood priming, avoid blood exposure, sensitization, and even potential infections from the donor supply.

Dr Pam Peeke: This is excellent. Could you talk a little bit about the US HF20 study itself and what were the endpoints?

Dr Stuart Goldstein: So the HF20 study, which was funded by Baxter was a five-center prospective multi-center study of the use of the HF20 for children who were 8 to 20 kilos in size and required CRRT as part of their standard of care.

The platform is a Prismaflex platform, which can use filters of larger size, but is also programmable for the HF20. And the goal was to enroll about 20 patients across five centers with two major endpoints. One was efficacy and the efficacy was determined with the FDA to be a 38% reduction in blood urea nitrogen over the first 24 hours of CRRT therapy. And then the second were safety endpoints in terms of tolerability, hemodynamic tolerability, platelet counts, anemia, et cetera.

And what we found was with the first 17 patients treated, 100% of the patients had 38% reduction in blood urea nitrogen, and we found this to be an incredibly safe filter. There were no allergic reactions. There were no device-related, unanticipated complications or serious adverse events. And we published our experience with the US HF20 study in the Journal of Pediatric Nephrology in 2020. Dr. Raj Munshi is the first author of that paper.

Dr Pam Peeke: Excellent. What clinical gaps specifically does the HF20 address? And why are these so important for children?

Dr Stuart Goldstein: The gaps are in the software that is used for the HF20 allows more precise fluid balance parameters, instead of larger changes, say, in fluid removal in mils per hour. There are smaller increments, allows us to be more precise for smaller kids. Again, we don't have to blood prime the circuit as often down to about 11 to 12 kilos. And so we don't sensitize patients to different blood antigens and we don't cause the iron overload that's often associated with repeat blood priming.

And what I can tell you, Dr. Peeke, with this filter with the HF20 study, the way the study was designed was that children would only be able to use the HF20 as the first filter during the CRRT course. As you know, patients are often on CRRT for many, many filters for many, many days. And when we had to switch away from the HF20 to larger filters, the bedside nurses, clinicians, and the parents were incredibly dismayed that we had to go to a larger filter and then blood prime for the patient. So what it also does is really demonstrate that there is a filter and a technology that's really made for these patients, which is what they deserve.

Dr Pam Peeke: Give us some examples of what would put a child in this kind of the need for CRRT, just kind of go to that place.

Dr Stuart Goldstein: So about 27% of all children admitted to an ICU around the world and we demonstrated this in a multi-center study called AWARE, which was published in the New England Journal of Medicine. We demonstrated that 27% of children develop acute kidney Injury. And this has also been shown by David Askenazi in the neonatal AWAKEN study.

And we also demonstrated that the development of a doubling of serum creatinine or 12 hours of oliguria are independently associated with mortality in children. And these are novel findings. It's been very difficult in adults to disentangle the chronic co-morbidities of COPD, obesity, diabetes, chronic kidney disease. Children generally don't have these co-morbidities, so this really demonstrated that acute kidney injury is key in mediating the mortality and also length of stay, time on the ventilator. And requiring renal replacement therapy also was one of the most predictive factors for 28-day mortality.

The number one cause by far just like in adults is sepsis. Number two, are shock both with and without sepsis. And number three are the additive effects of nephrotoxic medications that are often needed to treat the underlying diseases. What we're learning is starting renal replacement therapy earlier in children at earlier levels of fluid overload and accumulation may be associated with improved outcomes. But when you don't have a technology that is designed specifically for smaller children, there may be a reticence to start CRRT earlier.

In children, as opposed to adults, continuous renal replacement therapy is the most common initial therapy for critically ill children with acute kidney injury. And so we really needed to support these children while their kidney function hopefully recovers and they recover from their underlying illness.

Dr Pam Peeke: What has been your own experience with utilizing the HF20?

Dr Stuart Goldstein: So we utilize the HF20 as part of the study. And then Baxter received an emergency use authorization for the HF20 during the COVID pandemic. And what was important about that EUA was that it was not restricted to patients with COVID. It was really just restricted to small patients with acute kidney injury. And I think that this was done to get some more evidence. I think the reason the FDA did this was to get some more evidence about the HF20 and to be able to use this device, especially even in adults and in small adult patients, because they don't have a device that's specific for them.

So we have been using the HF20 quite frequently during the pandemic and are continuing to do so. And we've received another grant, from Baxter to develop a registry for all of the centers in the United States that are using the HF20 during the pandemic. So we can hopefully develop enough data that this can be used for once the pandemic is over for small children.

The filter works incredibly well for the intended use in that age group. We've learned that we may need to be a little bit more aggressive with anticoagulation with the HF20, because the blood flows are slower, the filter is smaller, so the risks for clotting may be a little bit higher. But other than that, we haven't seen anything that we've had to do in terms of changing our practice. We've now been able to treat these kids as aggressively as we do larger children.

Dr Pam Peeke: So have you seen changes in morbidity and mortality with using the HF20?

Dr Stuart Goldstein: It's too early to tell that, Dr. Peeke. And that's what we're hoping to see in our larger study under the EUA. So I don't have those data to be able to tell you that currently.

Dr Pam Peeke: But you're hopeful.

Dr Stuart Goldstein: Yes, I'm very much hopeful. So what an earlier collaborative that I ran called the Prospective Pediatric CRRT registry group demonstrated with Dr. David Eskenazi as the first author was that survival was lower, about 40%. ICU survival was about 40% for kids under 10 kilos and was 60% for kids over 10 kilos. And we're very hopeful that this technology for this weight range between 10 to 20 kilos will be associated with improved outcomes for sure. That's our hope.

Dr Pam Peeke: Excellent. And if you were to improve that HF20, what would you do? What more do you want from this technology?

Dr Stuart Goldstein: What we would really like is to be able to have smaller filters for other types of therapies using, say, the Prismaflex backbone. There are other extracorporeal therapies that are filter-based. A number that many of us are working on, which would be great to be able to package in with the HF20. That's what I'd really like to see, something Dr. Ronco calls multiple organ support therapy. Nephrologists who do critical care nephrology and intensivist who do CRRT are really experts. And most importantly, the nurses are really expert at handling these extracorporeal therapies. Now, we'd love for it to not take 20 years for smaller filters with these varying technologies to be available for kids in the United States.

Dr Pam Peeke: Fantastic. And any last words of wisdom to your colleagues out there who may be new with this technology with HF20? Any thoughts?

Dr Stuart Goldstein: What I would say is don't be afraid. There is a whole community out here in pediatric acute care nephrology, where we are willing to share our protocols, our thoughts, what we found that has worked. And not to say that what we do is say the best in Cincinnati, but we know why we do what we do. We know what has worked for us and not and the community. And the PPA KI research group, one of our missions is really to help educate centers that are thinking about starting up and providing resources so they don't have to reinvent the wheel. They should learn from our successes as well as our challenges and mistakes that we've made in the past.

Dr Pam Peeke: Fantastic. And you know, what is very clear is you have articulated the use of the HF20 and its value in the intensive care therapy of children, where before we did not have this kind of technology and it most definitely impacted morbidity and mortality. So thank you so much for sharing your wisdom and people can reach out to you if they have questions, yes?

Dr Stuart Goldstein: Anytime. They know how to find me. It's easy.

Dr Pam Peeke: So thank you so much, Dr. Stuart Goldstein, for sharing your wisdom about the HF20, its use and its history. And this concludes another edition of the iCritical Care podcast. For the iCritical Care podcast, I'm Dr. Pam Peeke.

This podcast is sponsored by Baxter Healthcare Corporation. When you choose Baxter for your CRRT program, you're not only choosing true patient-focused treatment with industry-leading CRRT technology, you're also selecting a partner dedicated to optimizing your clinical success in treating patients with acute kidney injury. Our commitment to you starts with the program individualized to your facility's needs and provides complete support every step of the way. For more information, visit us at www.renalacute.com.

Baxter Healthcare Corporation has provided funding for this podcast, but all content was developed independently by the presenter. Therefore, the views expressed on the podcast are those of the speaker and should not be attributed to Baxter Healthcare corporation.

For prescription use only. For the safe and proper use of this product, please refer to the operator's manual.

Pamela M. Peeke, MD, MPH, FACP, FACSM is a nationally renowned physician, scientist, expert and thought leader in the field of medicine. Dr. Peeke is a Pew Foundation scholar in nutrition and metabolism, Assistant Professor of Medicine at the University of Maryland, holds dual master's degrees in Public Health and Policy, and is a fellow of both the American College of Physicians and the American College of Sports Medicine.

Dr. Peeke has been named one of America's top physicians by the consumer's research council of America. She is a regular in-studio medical commentator for the National Networks and an acclaimed TEDx presenter and national keynote speaker. Dr. Peeke is a three-time New York Times bestselling author and is a science and health advisor for Apple.

The iCritical Care podcast is the copyrighted material of the Society of Critical Care medicine. And all rights are reserved. Statements of fact and opinion expressed in this podcast are those of authors and participants, and do not imply an opinion or endorsement on the part of the Society of Critical Care medicine, its officers, volunteers or members, or that of the podcast commercial supporter.