Episode Transcript:

Dr. Maddux: There are many obstacles to transplantation for individuals living with kidney disease, ranging from barriers getting on waiting lists to organ rejection. In this episode of dialogues, nephrologist Dr. Sumit Mohan, Associate Professor of Medicine and Epidemiology at Columbia University, joins us to discuss strategies to address inequities in access to transplantation, and why transplantation remains a vital therapy option for people living with advanced kidney disease. Welcome Sumit.

Dr. Sumit Mohan: Thank you, Frank.

Dr. Maddux: Maybe we should start a little bit with a question of organ availability and why it is the United States have a different organ discard rate than many other countries that have successful transplant programs.

Dr. Sumit Mohan: Well, so that's a that's a complicated question. And so let me start with, A: we have the largest organ allocation system in the in the world, right we have a multi layer deceased donor allocation system that goes from, or at least used to, go from local, to regional, to national. And a large focus of the transplant system in the United States has been on trying to ensure that we have good outcomes post transplant. And so what that has led to is a system where there is increasing selectivity, in selection pressures, in terms of who we transplant, and which organs we use for transplantation. And so what that selection pressure essentially does is it creates this incentive to try to use the best organs for you know, the patients who are going to give us the best outcomes as opposed to... So we're comparing organs against each other as to looking at organs for for the quality that they would provide a given patient. Right. So it's changed the paradigm a little bit. And so it has made it easier for transplant centers to decline organs when they're offered to their patients, leading to their ability to be declined. And so when multiple centers decline an organ, it's not surprising that eventually it's going to end up getting discarded.

Dr. Maddux: Yeah, it's a complicated process, I think, to recognize that there may be some unintended consequences of how transplant centers are measured in outcomes and their interest in taking as many organs as possible, I would assume.

Dr. Sumit Mohan: Right, no, you're absolutely right. So that it is an unintended consequence. I think the the idea that we want excellent outcomes post transplant is is not something any of anyone would argue with. But if you look only at one part of the process, right, it is going to create pressures on other parts of the system in ways that we never anticipated. Right? And so, for example, we have a multi step process that goes for somebody who's starting out on dialysis to getting to transplant they have to be educated, evaluated, waitlisted. And then yet we you know, that that entire process has no scrutiny. It's it's complicated blackbox. And so when you focus only on one part of the system, the rest of the system has unfortunately taken a hit.

Dr. Maddux: Yeah. And I would assume the waitlisting policies follow a similar tension. Where if you waitlist more patients, and then you have, and you're measured on outcomes and number of kidneys that are actually transplanted. My guess is there's also a tension in the performance metrics of the waitlist, and the actual support of the program. Do you see a any conflict there?

Dr. Sumit Mohan: No, absolutely. No. So part of this conversation around unintended consequences has been, how do we move away from, you know, looking at just an isolated post transplant metric, right. And so, this has been an ongoing multi year debate. One of the proposals on the table currently is looking at weightless mortality. Our fear is, by introducing weightless mortality into the kidney transplant system, we're going to discourage transplant centers from being open to waitlisting patients because they are now going to be faced with the regulatory burden of ensuring low mortality on that waitlist, which will create more selection pressures, which is likely to have some unintended consequences in terms of access to transplant. And while transplant centers don't have consistent selection criteria, while there remains this blackbox in terms of which transplant centers are using which criteria, I think this is going to get harder and harder for patients if we're not careful about what metrics we choose to use.

Dr. Maddux: Yeah, I agree with that. I've had some conversations with our one of your colleagues that that you know, in our head of transplantation, Dr. Ben Hippen around whether there might need to be sort of the final waitlist and then sort of the on deck waitlist, and this concept of potentially having a shadow waitlist that brings people to a point where they're really ready, but they're not in that final pathway of expecting a kidney in the next few months. Just curious what your thoughts might be on that.

Dr. Sumit Mohan: So unfortunately, that probably already exists in a way that is not patient friendly. Right. So the way the transplant system is set up is people get referred to a transplant center they get evaluated get waitlisted when you are on the waitlist you only receive an organ offer when you are active. Patients frequently don't even know when they are inactive or active. You know that there is this large gap of information and communication between patients are on dialysis or waiting for a transplant, versus patients who are active and have everything ready and are receiving organ offers. Even for those patients who are active and receiving organ offers, they are unaware of when they receive an organ offer, and our transplant center declined it without their... without telling them. The challenge there is there is now the shadow idea where transplant centers instead of inactivating a patient, may do what's called an internal hold. So rather than inactivating them turning off the active status, preventing that patient from receiving organ offers while they are recovering from a pneumonia or some sort of brief hospitalization, that they're temporarily inactivated. So they're continuing to receive offers, but nobody's communicating that. And so that has just led to increasing inefficiency in the system. So we already have a shadow waitlist. Now, you know, we're also holding many people responsible for ensuring that patients have dialysis patients that are furred and that we have a high prevalent population on the waitlist that is now going to collide head on with this weightless mortality measure. And it'll be interesting to see how this plays out.

Dr. Maddux: Yeah, very interesting. Let's shift gears for a few minutes and talk about organ availability and Oregon discard rates on the weekend, and why you think there's a weakened effect that's been seen in sort of availability of organs and, and let that dive into a discussion on the variability between various OPOs that we see across the country.

Dr. Sumit Mohan: Right, so you know, so this was a finding we, we had many years ago, where we, we were looking essentially for this idea of when organs are discarded, you know, is that a usable set of organs that we shouldn't be discarding? Right. So that that's that became a primary question. And as you can imagine, not surprisingly, some organs are not usable, even after procurement, right, either because they get damaged, or there is some sort of injury during procurement, or something happens during transportation. So while I think some organs will need always to be discussed, the question became, what proportion of the organ that were discarded in the US are actually usable? And so when you ask that question, one of the things that we had to try to do is to remove organ quality from that from the mix. And so when we, one of the things that we tried to do was look to see if there were differences by day of the week, because we know more causes of death vary by day of the week, that's a well known fact. And so what we found in this analysis was that as you approach the weekend, organs procured on a Friday or Saturday that would ideally be transplanted Saturday or Sunday, the risk of organ discard goes up by 20%, even after you adjust for organ quality. Now, I will say that, you know, lots of people didn't really believe our findings to begin with, right? Not surprisingly, they were like, wait a minute, this is real. I mean, you know, the phenotype of the lady transplant surgeon doesn't exist, like people become transplant surgeons because they like the adrenaline rush, and they like working in the middle of the night. But it's a real phenomenon, because we've also gone back and looked at organs that are used to see how successfully and how easily they're placed. So organs that are accepted for transplantation on the weekend, on average, require more offers before the transplant center is willing to accept. So we go further down the weakness before we find the right patient to take those organs. So clearly, there's an effect on the weekend. Whether that is a function of resources is unclear, because actually, we're finding that the larger transplant centers are more likely to say no. So clearly, there's an effect, what the cause of that effect is unclear. But the cause of that effect on patients is very clear. And by that what I mean is this, when we look at transplant centers across the US, there is a wide variation in the probability of transplant. So if I got on the waitlist today, depending on the transplant center, I got on my probability of getting a kidney transplant within three years of getting on that waitlist varies from 4% to 64%. It's an enormous amount of variation, it's a 16 for variation, something that we wouldn't accept in any other form of any other aspect of medicine. And so the question becomes, "why is that?" right, so, the common, you know, logic has been Oh, there's a there is a variation in the organ supply. The different opioids are effective to different extents, and so that has contributed to this large variation in in access to transplant even after you get on the waitlist. And I would argue that that's not the case. When we look at or transplant centers within a single OPO, right, with single donation service area, you may find 7,8,9 transplant centers on occasion. So for example, New York City has nine transplant centers in a 10 mile radius essentially, in a single OPO. And the way the organ allocation system used to work at least, was that organs made available within that donation service area by that OPO first. Those transplant centers got first dibs. So those transplant centers technically have all have equal organ supply. And yet, that's a seven fold variation in the probability of transplant with the just those transplant centers. So it's not Oregon supply, it is Transplant Center decision making. And so I think it is important that we start to have greater transparency in how transplant centers make these choices. What is influencing whether they take an organ offer for a given patient or not? What's influencing whether they list a patient or not? So that our patients can make informed choices about which transplant centers they want to be listed at.

Dr. Maddux: So it's a it's a governance issue that you're really talking about here? It's the governance of how a transplant center accepts or declines in organ? And I'm interested in is that decision making strictly in the hands of the transplant surgeon? Is it a broader group? Does the patient or their you know the the patient themselves get a play in that particular decision making? I'm just curious with perspective on that.

Dr. Sumit Mohan: So you know, it's a complicated process, but it's a very time limited process, because if a center is going to say no to an organ, the clock's ticking, and we need the next center to use that organ, so each center gets about 60 minutes to make a decision. It's a very quick decision. There is usually a defined person in the vast majority transplant centers in the US it is the transplant surgeon. There are some large transplant centers that do have nephrologist taking organ call and making these decisions. And to be completely honest, given the time crunch, unless you're going to say no patients don't find out about these or sorry, unless you say yes, patients will find out about these organs in real time if I if I as a surgeon except in organ, then I have to get my I have to call the patient have make them aware of the organ offer. Have them say yes. If I'm saying no, we don't tell patients today, that's the norm. Our patients part of the decision making they are to some extent. So when we look at high risk organ we look at hepatitis C positive organs or, you know, organs for older donors, we have patients opt into those sort of less than ideal organs to begin with. But they're not part of that decision making process subsequently. Right. And so if a patient's preference changes, are they aren't given the opportunity to go back what other options exists? Right. And so what we've been proposing is this idea of asynchronous shared decision making is idea that patients should have a say they should be made aware, we recognize that it's a it's a complex decision that cannot be shared in real time. But I think there are ways that we can share the decision after the fact help patients understand the choices of transplant centers make and have them, you know, be in agreement. And if it's not in keeping with their preferences, you know, it creates the opportunity for a patient in their transplant center to communicate about what it is that they wouldn't have, but rather had happened.

Dr. Maddux: Do you think there's an opportunity to create sort of preemptive preferences of patients into a series of categories. I'm a patient who may be interested in accepting a high risk kidney, because it's so important for me to get off of dialysis right now, or something like that. Is there a way that you could categorize patients in advance? So that the surgeon or the team making that decision has information about what's acceptable? Or what's more likely to be acceptable to a patient given their current condition?

Dr. Sumit Mohan: Right, so that's, that's a very good question. And I think part of the challenge there has been kind of categorizing organ quality and trying to think about how we do that. I think one of the things that we did several years ago now in the allocation system was you know, as A broad system that we introduced a composite measure of organ quality within with the idea that A: it would help decision making and B: it would help us identify these less than ideal organs and have patients opt into them. The primary problem with this system right now is that it's a percentile ranking. So what ends up happening is I rank in organ, not based on the benefit, it brings patients, but relative to other organs. Right? So if I have a less than ideal organ, that is in the 90th percentile, yes, 90% of the kidneys procured in a year are better than that organ. But for the right patient, it still represents a enormous survival benefit and an improved quality of life, right? And that that gets completely lost in translation. Because what you're telling me is what you know that if you go into a grocery store and say, you're looking for strawberries, and I say, You know what, 90% of the strawberries are better than the ones that I'm about to hand you, you're not going to pick them up, even if they're perfectly fine strawberries, and you're planning to have strawberries today, and you're going to eat them up, and you want them to last four days, right? And so that's kind of where we're at where we're at. We're making the wrong comparisons. And once we start making the wrong comparisons, and we don't talk about value to patients, it's hard for patients to make those choices.

Dr. Maddux: Do you think the transplant community is ready to actively have an honest conversation about that issue and begin to address it in the way they evolve policies?

Dr. Sumit Mohan: I think so. So I think there are several measures afoot. There is an effort from HERSA and SRTR to relook metrics in the way transplant centers are being measured. Right. It's this effort called the Task Five. And hopefully, we'll have, you know, early results from those conversations in July and August, this later this year. I think that is a general recognition that we need to take organ choices in the context of what it offers patients. And so thinking in terms of developing clinical decision support tools that help centers say, "wait a minute, if I have an organ offered today, and I'm declining it, I have to do it in the broader context of recognizing I have a burden hand versus two in the bush", right. So a transplant center would say no to an organ with the idea that this patient is going to get a better organ, in a relatively short timeframe. And if that's not true, which it frequently is not, then saying no, is the wrong answer. Right. So we're trying to develop these clinical decision support tools to try to help people understand what are the you know, whether it makes sense for patients to decline the organ offer that you haven't had for them?

Dr. Maddux: You know, I'm sure there are models both... We do mathematical, physiologic models, but there are probably also economic modeling tools that could be used to wreck to look at not the economics of this, but actually to look at it from the standpoint of where the greatest impact for the patient actually is. And there are probably techniques that exist. And I know that some of the economists that developed the paired, you know, the period organ availability, and the paired donation rules have done some remarkable work on looking at how to model patient behaviors. With regard to that. I just wonder if there isn't some opportunity here?

Dr. Sumit Mohan: Oh, there absolutely is. Right. The challenge has been and this has been something that we've been working on for a couple of years now is to say, can we develop a clinical decision support tool that lives using a model that allows us to predict a what is the benefit of this organ today? Versus a, you know, whatever the next offer is, right? So we should in order to be able to do that we need to model out, when's the next offer going to show up? And the probability that that next offer is actually going to be better than the offer that you're getting today in terms of quality. So it's a complex problem, in part because the longer somebody spends on dialysis, the same quality organ, you know, provides smaller benefit. So the so those two are not independent variables, they tend to interact with each other. So it is a complex math problem, but you're right, it's not an unsolvable problem.

Dr. Maddux: So I want to shift to another area but first, I want to just let you just explain to the viewers here today. What do you think the upcoming changes are to the organ allocation system and and what do you think we might see in just the near future.

Dr. Sumit Mohan: So the most recent allocation change is what we call the concentric circle or circular allocation. Which is in order to remove geographic disparities, and this idea that organ allocation is a function of where you live. The allocation system is moved from specific donation service areas to suit to circles. In other words, meaning the closer somebody lives to a donor hospital in a circular area, as opposed to an arbitrary boundary, they get some priority points for that organ. So anybody who lives within two or 50 nautical miles of a donor hospital, you get some additional points because it's easier to get that organ to them. This is a stepwise process to getting to the final goal, which is that everybody in the country will have what we call continuous distribution, which is equal access to all organs. We have to account for distance between when an organ becomes available where the patient is just because we have to get physically move the organ from there to that patient. So there will always be some kind of scoring or priority for people who live closer to where the organ is. But the idea is these arbitrary geographic boundaries for regions and donations or raise will go away. The challenge here is that when we are due this, the complexity of the system is going to dramatically increase. So in our first step, where we've gone to circular- the circles, we've seen an increase in coal this time. And then unfortunately, we've also seen a dramatic increase in organ discard. So what used to be a one in five discard rate 20% discard rate in 2021, has suddenly gone up to 25%, meaning that one in four organs are being discarded, that number is close in the earlier part of 2022 appears to be 27-28%. That is really problematic. In my view, it's it represents a large number of kidneys that are potentially usable and could be used to save lives, extend lives improve quality of lives for 1000s of our patients. And so while we're women, this move towards continuous distribution, we have to keep an eye towards utility off the organ supply and making sure we're good stewards of what is essentially an incredibly valuable but scarce resource.

Dr. Maddux: It seems like there are opportunities for us to improve our preservation solutions, our opportunity to try to reduce the impact and or mitigate the impact of coal ischemic time if you're going to try to make this broader distribution a reality and not discard a lot of organs.

Dr. Sumit Mohan: Absolutely, I think that the science is in its infancy, but I think the opportunity for improved organ preservation reconditioning of organs, you know, are are enormous, right. Xenotransplantation is a nother aspect of what I think people are excited about in transplantation today. But the I think the opportunity for good science here is quite large.

Dr. Maddux: Yeah. Well, while you bring it up, I want to cross two thoughts. One is inequities in transplantation are substantial, both predominantly with living donor transplants. And some of that is cultural, some of that's probably the system of care and other health equity related issues that we have in this country. But the opportunity of xenotransplantation really sets forth the potential that organ supply and organ availability could decades from now be fundamentally different than it is today. Just some thoughts about that from your perspective.

Dr. Sumit Mohan: No, absolutely. Right. So if you if xenotransplantation becomes a reality, which you know, with the recent, the heart transplant and Maryland, the kidney transplant both at NYU and UAB, I think this has been an exciting time. If we are able to cross that barrier, and we no longer have quite as tight a organ supply system, it certainly creates the opportunity to radically change what we are able to do for our patients, right radically change inequities in the system. Because then we're not talking about a constrained organ supply system. And so there is no reason that anybody who needs an organ isn't able to get one. So it is it's definitely an exciting development and hopefully, something that we'll see sooner than a decade away.

Dr. Maddux: Yeah. It'll, it'll be interesting to watch that that field evolve and, and become part of a broader discussion, which will include ethical components to the discussion. It'll include issues around society and how we look at making life saving treatments available, this being sort of the lead one for kidney disease. Any final comments just about how we've looked at the the issues of inequity in access to transplant care and transplanted organs?

Dr. Sumit Mohan: So, you know, inequity is is a major concern, right? It's, if you are going to have a kidney allocation system of any kind, whether it's, you know, transplantation or human scarce resources. The fundamental cornerstone of any system is that people have to believe that is it, it is inherently fair. And the minute people stop believing that a system is inherently fair, fair, it stops working as intended. So as much as you know, I am disturbed by discard rates. And the fact that, you know, utility has, you know, is a competing with equity, I think we can't let go of equity. That's the one thing I will say that we need to make sure that equity remains a cornerstone of anything that we do and develop. That's one, the other pieces, I will say that we have been quite effective at how we have moved on the equity scale. So which starting from recognizing in the early 2000s, changing the way we we prioritize based on how organ or match to the most recent changes in 2014, where we moved from allocation time starting when you added somebody to the waitlist, as opposed to when you started somebody on dialysis. That major shift was done with the primary intent of mitigating disparities, and it has been remarkably effective. So if you look at the most recent data, it looks like we've made tremendous progress on that front. Doesn't mean that we have completely solved inequities and kidney transplantation. But the extent to which we have been able to successfully narrow them down onto the deceased donor transplantation side, I think gives me hope that we can do this right, in other parts of both kidney transplantation but kidney disease more broadly.

Dr. Maddux: Okay, any final comments for our audience today, just on your perspective of what some of the critical issues are around organ availability and and transplant access to care before we finish?

Dr. Sumit Mohan: That's a very broad question. So I would say that this is an exciting time for kidney transplantation. I think there is broad recognition that it is the preferred treatment choice that we have gotten to the point where patients do remarkably well. Long term outcomes are are improving very quickly. So I think the onus is on us as clinicians to make this more widely available to our patients, whether that means getting more people waitlisted whether that means encouraging more people to become organ donors, living or deceased. And hopefully, you know, with xenotransplantation, if it's truly around the corner, hopefully that will be a real game changer for our patients.

Dr. Maddux: So my guest today has been Dr. Sumit Mohan, we've been talking about transplant care and organ availability and many of the aspects of this area of taking care of people with advanced kidney disease. Sumit, thank you so much for joining us today.

Dr. Sumit Mohan: Thank you, Frank.