Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And today, we're highlighting normothermic machine perfusion or NMP for kidneys. Joining me is Dr. Jacqueline Garonzik Wang. She's the Division Director of Transplant Surgery and the Co-Director of the Comprehensive Transplant Institute at UAB Medicine. Dr. Garonzik Wang, thank you so much for joining us today.

To start, I'd like it if you framed the problem for us. We know there's thousands of patients that are waiting for kidney transplants, yet a significant number of donated kidneys are ultimately discarded. They're not able to be used, maybe a donor, a recipient—who knows the reason? Why does this happen? What have you been seeing in that space?

Jacqueline Garonzik Wang, MD: Well, thank you for the kind introduction. This is a topic that I'm quite passionate about, so I'm excited to be here today to talk about it. As you alluded to, we have tremendous disparity between the number of people that are waiting for an organ transplant and the number of organs that are available.

So currently, in the United States, there are about a hundred thousand people on the kidney transplant waiting list. And despite that, we only do about 20,000 to 30,000 kidney transplants per year. Even though we are nowhere near meeting the need, there is this group of kidneys that are recovered with the intent for transplant, but then end up going non-utilized. And it's not a small number. In 2024, that number was about 9,000. So, 9,000 kidneys that were non-utilized, and that's not a small number. That kind of number is what keeps me up at night. You know, I have these patients that are waiting, I'm desperately trying to get them transplanted safely. What can we do to address those organs that might be available today that aren't being utilized?

And I think when you think about why those organs aren't getting used, I think there are kind of there are a lot of reasons, but there are two kind of major categories or reasons that are potentially addressable by utilizing something like normothemic machine perfusion.

So, the one kind of category is I would call the inefficiency in our allocation system. So, in the United States, organs are allocated to recipients in a fair and equitable manner. There is this large waiting list, and we go down that waiting list patient by patient to see if the kidney is suitable for that patient. And that can take a long time. And sometimes, if you have a kidney that's kind of already hard to place by the time it finds its home, it's already been out of the donor for too long of a period of time and there's uncertainty about whether or not that would be suitable.

The other category, which I would say is a slightly larger one, is organs that I think in general we are just uncertain about their suitability. So, we assess donor suitability based on a large number of clinical data, whether it's lab values or things that we find in the donor that are happening around the time somebody is dying. And so, you can imagine that labs, and even sometimes biopsies can be somewhat abnormal or misleading.

And I think that if we are uncertain about the suitability of an organ, we tend to err on the side of being more conservative, which I think is appropriate. We don't want to take a risk in a human being. And so, I think if we're uncertain, we tend to pass. And while that's probably being conservative on behalf of our patients, in the same vein, I think that that means that sometimes there are usable organs that are going unutilized. And I think NMP can really help us address those two, I think, shortcomings of our current way that we allocate kidneys.

Melanie Cole, MS: Well, thank you so much for explaining that issue. It is quite complex. And as we're thinking about it, Dr. Garonzik Wang, your team at UAB has recently begun partnering with a company that provides normothermic pumping for kidneys that have already been declined by multiple transplant centers certainly in hopes that they can pump to allow time to evaluate and possibly improve the function to the point that they can be transplanted successfully. Tell us a little bit about what sparked this initiative. tell us about this 'cause it's fascinating.

Jacqueline Garonzik Wang, MD: Yeah. So, I think this partnership has really been a game-changer for our patients and for the way that we think about kidney transplantation in the United States. so, I first began partnering with this organization. The organization is called 34 Lives. It's a public benefit corporation out of West Lafayette, Indiana, in my previous position, prior to joining UAB, it was one of the first few centers in the United States to participate in this endeavor. And I was really, really excited to bring it here to our patients at the University of Alabama.

What they essentially do is when organs exhaust allocation in the United States, the OPOs, which are the organizations that allocate these, can approach 34 Lives. And then, 34 Lives reaches out to their participating centers to see if we have any interest in the organ. If we express interest, then the organ gets transported to 34 Lives, and it's placed on a normothermic machine profusion, or NMP, for two hours.

And the beauty of NMP is it does a few things. One, it warms the kidney up to kind of near-normal, or near-physiologic temperature. And then, it allows the kidney to start functioning. So, it's really the first-time in the United States that we can assess the functional aspects of the organ after it's been taken out of the donor.

So, in warming it up, it kind of resets that cold time or the clock. So, it gives us more time. And then, it actually gives us functional data on how the kidney is likely to perform to kind of really help to reduce or get rid of that uncertainty and make us more confident in using this organ.

Melanie Cole, MS: Wow. So, it's essentially an effort to rescue.

Jacqueline Garonzik Wang, MD: Exactly.

Melanie Cole, MS: And expand that access, right? So as I understand it, Dr. Garonzik Wang, you've done several of these recently and are really excited about the potential for patients. For clinicians who may not be familiar with the technology, explain a little bit about how NMP works, because that's really the crux of this.

Jacqueline Garonzik Wang, MD: Yes. So, essentially, the kidney is hooked up to a device. There's a cannula that's placed in the artery. And that cannula is then hooked up to a machine that essentially pumps fluid through the kidney. That fluid is oxygenated and it has various nutrients and other things that are theoretically good for the kidney in it. And it allows the kidney to wake up, start utilizing that oxygen and start functioning.

At the same time, the ureter, which is the long tube that drains urine out of the kidney, that is also hooked up to a cannula. And the kidneys on the device actually start to make urine. So, that is one of the additional things that we look at to determine whether or not the kidney is suitable for transplantation. It's just another marker that the kidney is waking up, it's utilizing oxygen, it's functioning and metabolizing, and then it's clearing and creating urine.

Melanie Cole, MS: Wow, isn't that amazing? The technology that's happening right now and so quickly. So, how is it different from the traditional cold storage approach we've relied on for decades? And what kinds of information can you gather while the kidney's on the pump that helps you decide whether it's viable?

Jacqueline Garonzik Wang, MD: Yeah. So there are I think two kind of ways that, kidneys in the United States are cold stored. The first and most classic way is just on ice. So, the kidney is taken out of the donor. It's flushed with preservation solution. And then, it's essentially stored in a cooler and transported from the donor hospital to the recipient hospital. And it remains cold until it's put back into its new home.

There is an actual device that has been used for the past decade or so in the United States. It is a hypothermic pump or hypothermic machine perfusion referred to as HMP. And that has been used for a while. The difference I think between that pump and this newer device is, in that setting, the kidney remains cold and metabolically non-active. So while there is fluid being perfused through the kidney, it's not done so in a way where the kidney actually wakes up and starts working. So, it really gives us no functional information about the kidney.

There's, you know, some thought that normothermic machine perfusion prior to us utilizing it in the United States starting in 2024, was not really utilized in the kidneys, but it had been utilized in other organs. And I think it's one of the reasons why we were slow to get in the game with the kidneys, is because we did have this cold pump that had been so widely utilized. But, you know, as I alluded to, there are some shortcomings to that and specifically with Not really having any functional data about how the kidney is likely to function.

Melanie Cole, MS: Doctor, as you're getting into this and learning more and more about it, have there been moments at all where a kidney that seemed questionable initially begins to demonstrate reassuring function once it's on the pump?

Jacqueline Garonzik Wang, MD: Yes, I mean this has been a very humbling experience, and it's actually really challenged what I thought I knew about donor organ assessment. I think, when I kind of started in my early experience with this, my goals really were to utilize those kidneys that I would've otherwise used, but they got offered to me so late in the game that it was too late to accept it. It's coming from across the country, and it's been out of the donor for 24 or 36 hours.

To me, NMP was the perfect solution to prevent those usable kidneys from going unutilized. But as we've gotten more and more comfortable with this, I think we've expanded the clinical criteria for the donors that we assess. So for example, an older donor I might not have historically, you know, in extremes of age, considered utilizing that kidney. But now, I can let the pump decide for me. I can accept it and put it on the device, and the device will tell me how likely that kidney is to function. And we've been able to safely really expand criteria of the kidneys we're able to utilize because we now have this functional data to kind of assess how the kidney might work.

Melanie Cole, MS: Wow, that's, I mean, really so pivotal to expand access to transplantation. And when we think of a patient perspective, Dr. Garonzik Wang, how meaningful do you see that this could be if it consistently allows transplant teams to utilize those organs that would've gone unused? If patients are waiting on that wait list, which we all know can be a long time and quite a critical time in a patients life while they're managing all their comorbid conditions that go into managing while they wait, what do you see as this approach for patient's perspective? Have you told patients about this?

Jacqueline Garonzik Wang, MD: I would definitely talk to patients about it. Most of them are very, very excited because most are sitting with the reality that they're going to sit and wait for a kidney transplant sometimes in some locations, anywhere from for five to eight years. And while dialysis is lifesaving, it is not without its own associated risks and the mortality on dialysis is real. We know that if we can transplant patients earlier, they are more likely to do better at the time of transplantation and less likely to die while waiting for a lifesaving organ transplant. And so to me, this symbolizes hope, the fact that we can get to our patients quicker, to decrease their waiting time to transplant them when they're healthier, potentially even before they go on to dialysis. So, they don't have to realize the effects, the downstream effects of dialysis. These are all opportunities for us to help patients earlier, so they wait for shorter periods of time.

Melanie Cole, MS: Really what it's all about. How about the use of higher risk donor organs? And we've been hearing a little bit about this on and off for years, but you mentioned older donors or donation after circulatory death donors or you know, disease-affected donors. Would this expand the use in that space at all?

Jacqueline Garonzik Wang, MD: Oh, certainly. I think, we just don't have enough kidneys to go around. So if we sat and waited for perfect, young, healthy, brain-dead organ donors, none of our patients would ever get transplanted. Fortunately, there are not a lot of young, healthy people passing away. So, it's a good thing. But it definitely challenges the donor pool. And so, we have to look at every single organ, you know, no matter what medical comorbidity or what is going on with that donor, and say, "Is this something that can provide survival benefit to my patient?" And in that vein, I think both as providers and patients, we take a lot of shared risk together to try to help get our patients transplanted. And this is really one of the first times where we've had a significant jump in additional data to help decrease the risk associated with a certain decision.

For example, we may label an older DCD donor as higher risk. But our current risk stratification metrics aren't great. And there are subcategories of that, those same exact donors that would work perfectly fine and subcategories that wouldn't. And so, by putting kidneys on NMP, we can suddenly get so much more additional data that, in my mind, takes the risk away in our decision-making. You know, like in anything in life, why wouldn't you want more information and more data about how likely something is to work or to be for you?

So, to me, of all the risks that we take, this actually feels like this is kind of stepping away from riskier decision-making and getting more data and making a more informed decision.

Melanie Cole, MS: Amazing. If we were to look ahead, how do you see machine perfusion evolving, do you think it could eventually move from simply evaluating organs to actively treating or even repairing them while they're on the pump? What excites you the most about the potential impact of this technology for patients?

Jacqueline Garonzik Wang, MD: Oh, such a great question. I mean, I think we are really just beginning to see the tip of the iceberg of the impact. When we kind of started this endeavor, our goal was to safely utilize kidneys that were at-risk for being discarded. We wanted it to be as safe as a standard kidney transplant.

I think in my mind, I never thought that it would potentially provide benefit. You know, I just wanted to safely utilize more kidneys. But we just recently published the data from the first 100 of these that were done in the United States. And what we saw when we compared them to matched kidneys that did not undergo NMP. We saw a dramatic reduction in delayed graft function of these kidneys. And so, delayed graft function is the need for dialysis within the first seven days of transplant. Sometimes, kidneys that are more marginal or higher risk can take a little bit longer to work. in the kidneys that underwent NMP, about 20% of them experienced delayed graft function in comparison to about 60% in the matched controls.

So, that was kind of our first signal that this wasn't just safe, but there actually might be some benefit to higher risk kidneys from undergoing NMP. So, we're currently in the process of looking into that. But if that pans out, you can imagine a world where every single kidney, or at least every higher risk kidney is placed on a device to get rehabilitated so that it isn't just functioning for our patients, but we're getting the most out of it, and it's functioning to the best capacity that it could function.

Melanie Cole, MS: Really an exciting time in your field. Dr. Garonzik Wang, as we wrap up, you've already performed several of these perfusions. What's that early experience been like for you, for your team? And what would you like other providers to take away from this fascinating conversation on NMP?

Jacqueline Garonzik Wang, MD: Well, I think, it's been really fun to bring it here to UAB with a group of really dedicated transplant surgeons who are really already working hard to try to get our patients transplanted. This suddenly provides an additional source of usable organs for our patients. And they've really, really embraced it. We went live with the program in the beginning of February. And we've already done over 20 of these here at UAB in the two months that it's been going. And that is because our team has really kind of seen the benefits of it. I think one of my partners, actually after the first two that he did, I think the quote that he sent to me was, "This is magic."

And I think it's because these are kidneys that we typically expect to have a rockier first course, and they're fusing beautifully and doing really well. So, the team is really engaged and really embraced it. And for me, as a leader, that's been really fun to watch and to support. And I think, you know, from a provider perspective, I think this technology is really allowing us to rethink what we think about what we think are the kind of margins for a suitable kidney and really expand the types of kidneys that we utilize so that hopefully we can provide more transplants to more patients, both here at UAB and across the country.

Melanie Cole, MS: Thank you so much, Dr. Garonzik Wang, for such a fascinating and enlightening discussion today. It really is an exciting time in your field. And thank you for sharing your incredible expertise for other providers. And for more information, please visit our website at uabmedicine.org/physician.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole.