My name is Mike Shilsky and I'm professor of medicine and medical director for liver transplant at Yale University. As the chair of the American Association for Study of Liver Disease Special Interest Group for Transplant and Surgery, it is my pleasure to introduce you to our distinguished speakers and co-moderator for this webinar entitled, Simultaneous Liver Kidney Transplant, How Did We Do With the New Criteria? We have two wonderful speakers today. The first is my colleague, Dr. Richard Formica, who is professor of medicine and medical director of the renal transplant program at Yale. He is currently president of the American Society of Transplantation and is a member of the UNOS membership and professional standards committee. As a former chair of the UNOS kidney transplant committee, Rich played a pivotal role in the crafting and adoption of policy on simultaneous liver kidney transplant. His partner in this presentation is Dr. Reeth Taro Hirose, real for short, who is professor of surgery in the division of transplant surgery at UCSF. He is also vice chair of clinical operations and value and the associate program director, UCSF general surgery residency program. He also serves as surgical medical director of the scientific registry of transplant. Rio was vice chair of the UNOS liver and intestine committee at a time when this policy was under review and was chair at the time of the policy implementation. It is also my great pleasure to introduce my co-moderator and colleague, Dr. David Mulligan, who is professor of surgery and chair of the section of transplant and immunology at Yale. David is the current UNOS president and is counselor at large for the American Association of Study of Liver Disease. David also previously served as chair of the UNOS liver and intestine committee at the time that Dr. Formica was chairing the kidney committee and their collaboration helped move this policy change to implementation. Today, we will hear a presentation from Drs. Formica and Hirose, followed by question and answer session, which Dr. Mulligan and I will moderate. Without further ado, I turn over this session to our presenters. Thank you, Mike. So thanks again. This is a wonderful invitation. And what myself and Rio would like to do is to spend an hour going over the concepts and the rationale behind developing the policy, let you all get an understanding of the data that was used and the thought process, and then Rio will walk us through what the outcomes of the policy have been and hopefully frame the conversation for our question and answer session. These are our conflicts of interest. We both have fiduciary roles that intersect with organ allocation, but neither one of us has any financial conflicts. So I want to start off with this slide. This two year data report is publicly available to anybody who wants it. And as a spoiler alert, Amber Wilk has done a very nice two year analysis of this policy and the outcomes. And I know that that is in the first stage of revisions for hopeful publication in the near future. So anything that we're talking about today, you can also read when this manuscript is published. So here is our this, for those of you who are familiar with the bucket lists for kidney, this is actually updated in 2020 to include acuity circles. But as you can see, we have a prioritized algorithm for allocating kidneys of various qualities to individuals who the kidney committee has deemed in order of priority for urgency. And I want to also point out that on this table, you'll see inside circle safety net. So the safety net has been brought over to the new kidney allocation system. However, it still remains that multi organ allocation comes prior to any allocation of single organs. And although the liver kidney proposal and system that's in place gives medical eligibility criteria, the fact that multi organ allocation comes ahead of other organs without any without any triage of acuity or a medical need still exists. And by and large, this has been the transplant communities approach this. We don't want to hear about it. We don't want to talk about it. Let's pretend it doesn't exist. However, committees are now at work within UNOS to begin to address this larger problem. But just to reiterate, the combined liver kidney allocation system is not looking at that larger problem. It's this part of the challenge has been it's a two class system. So if you need a liver and a kidney, you preferentially get access in terms of coming first. And you also get preference in terms of organ quality. And that leads to solitary kidney recipients to a second status or a second class status. So what was the problem that we needed to solve? And I think this graph is very representative and I want to spend a few minutes on this. So the number of liver kidney transplants has steadily risen over time. The slight decrease happened around the time of a prior consensus conference for medical criteria. But after a brief reprieve, the numbers continue to go up. And clearly that is partially reflected in the acuity of illness of patients who need liver transplants. However, it also is reflected in the fact that different programs would apply criteria in a differential manner. And it would be both different across programs. It would be different within US regions. An important point here, though, is when we were talking about this policy, we did not come at it from the entire perspective of hoping to stop the rate of rise. We would have considered it a success if we just blunted the rate of rise. So when Rio's walking through the data, I would like you all to keep that in mind. Here's another look at the way that kidneys were being allocated. SLK recipients, by and large, were taking up kidneys that were the better quality or the kidneys predicted to last longer, the low KDPI kidneys. And as you can see from this graph, nearly 50 percent of all organs of low KDPI were allocated to liver kidney recipients. And as it turns out, those kidneys would have primarily been allocated to children because children get priority for these kidneys with KDPI less than 0.35. And people weren't happy about this. And this was causing quite a bit of displeasure and particularly from the pediatrics community, a lot of calls for a more equitable approach. However, you need to acknowledge the fact that it appears that combining a kidney with a liver when the patient requires both improves outcomes. And here's this classic paper from Fong et al. Showing in the left panel allograft survival and the right panel is patient survival. You see that these mirror each other. The top line represents the SLK population and the bottom line is the liver transplant alone population. And although there are some critiques of this study, and I've listed a few of them in the lower panel, by and large, it appears that patients who receive a combined kidney liver transplant do better than liver transplant alone. And the bulk of that morbidity that the patient experiences occurs within the first year. After that, the lines begin to parallel. Now, this is an older paper from Jamie Locke. And I recommend that everybody who's interested in the topic reads this paper. Every time I read it, I get something else from it. What I'm going to focus on today is panels A and B. And in panels A and B, you see the outcome of simultaneous liver kidney compared to liver transplant alone, with the lighter line being simultaneous liver kidney and the darker line being liver transplant alone. And what these two panels do is divide the population into those on dialysis for less than three months and those on dialysis for greater than three months. And it was that panel B that made us all think, well, maybe we shouldn't be doing simultaneous liver kidney transplants because there did not seem to be a benefit. However, if you think about this, this population of patients is decidedly different. Those who have been on dialysis for greater than three months are chronic kidney disease patients. Keep that concept in mind. And those in panel B, these are those acutely ill patients who we all care for in the ICU. So they're on dialysis for less than three months because the acuity of their illness is driving a lot of their renal failure. So we wanted to begin to try to tease out those two populations of patients. OK, so the main challenge that we faced was developing medical eligibility criteria. And before I start to dive into this, you should all know that the public policymaking process requires compromise and trying to trade trade off risks and benefits. So as we go through this, I'm going to talk to you first about what we use to analyze the data. But ultimately, the final criteria were different. And that was through the policy reconciliation process. So the first thing is I'm going to I offer this to everybody. I don't claim many things as my own ideas, but this is a way that I've come up to explain kidney function to those people who don't understand it. So I want you to imagine that you're a bathtub and the faucets running and the drain is open. And in this example, the production of creatinine in your body is the drain is the faucet running. And this is affected by your age, your size, who you are, male or female, muscle breakdown, and to the extent that you can choose biological race over self-reported race. And that has actually become an important topic of discussion within the kidney community. Your serum creatinine represents the level of the water in the tub. And that level of water can be affected by how big the tub is, how small the tub is. So hyper or hypovolemia and anisarka. Remember that serum creatinine distributes in total body water. And finally, the clearance of creatinine is the drain being open and that there's either acute renal failure or normal renal function. So as you can see, in a liver transplant population, as our patients waiting for liver transplant, as opposed to the healthy population, many variables are changing in real time. Right. So our production of creatinine can be diminished because of disease and malnutrition. We have constantly changing volume statuses of our patients and renal function goes up and down. So it becomes very hard to really know what kidney function is based upon their calculated EGFR. So statin C clearance will make this a little bit better, but it won't get around some of these other problems of changes in volume and such. And I just reiterate those points on the slide. So there's another thing that everybody should know that acute kidney injury is very heterogeneous and it's an unpredictable condition. A lot of the problem lies with the underlying comorbidity of the individual patient. So why did they get kidney injury in the first place? By and large, when you look at the literature, I think we can comfortably say dialysis makes it worse. Most of my colleagues, we try not to dialyze kidney, acute kidney injury patients because we worry that we could perpetuate the injury. And those individuals who go on to need dialysis with acute kidney injury, about half of them die. And that's probably from the process that gave them the AKI. AKI due to sepsis. They don't recover from sepsis and they die. And those who do recover can take up to eight weeks. And any of you who have participated in the care of kidney transplant patients know that because delayed graft function patients, which is effectively AKI in a deceased donor kidney, can take up to two to three months before we declare a kidney non-functional. And I think it's important to note, and this was an ad hoc analysis done by one of the UNOS analysts at the time, that even when you get the kidney with the liver, the SLK recipient, delayed graft function requiring dialysis was occurring in up to 25% of the population. So we needed to reanalyze the SRTR data. So we quickly went through some of this. So the first thing is, if you receive an SLK prior to the policy, upwards of 60% of the individuals were already on dialysis at the time of the transplant. And of those individuals who weren't on dialysis, 55 to, you know, let's say 55% or 45% of those individuals had serum creatinines greater than 2.5. The number 2.5 was chosen because if you do an MDRD calculation, it comes out between 30 and 35 mLs per minute. So in order to define acute kidney injury, we started to look at the demographics of who was receiving SLKs already. You look at the individuals who are on dialysis and for the duration that they were on, you can see that whereas 60% of the individuals may have been on dialysis, perhaps only 40% of the individuals were on dialysis for more than two months. So putting into context that time you need to wait to recover kidney function in acute kidney injury. So for the purposes of analyzing the data, we defined acute kidney injury, or we defined kidney failure, let me rephrase that, kidney failure as a serum creatinine greater than 2.5 or dialysis for more than eight weeks. And we tried to reanalyze the data to see what we got. And a couple of things came out of that. So the top curve is the top panels reflect the renal failure group and the bottom panels reflect the individuals who would not have been defined as renal failure by our criteria. And what you can see in the top, if you had our definition of renal failure, in fact, you did appear to do better with an SLK than receiving a liver alone. And I included the demographics to the right there. You'll note that these patients did have, the SLK patients had a lower MELD score. That's probably the big takeaway point from that. However, if you look at the other group, the group that did not have renal failure by our definition, you actually did better if you got a liver transplant alone. And when you look at the demographics of that group, it appears that the liver transplant alone individuals were less ill than the patients who were given an SLK. And this started the thought process that perhaps what's driving a lot of the outcomes in SLK patients is the underlying disease state of the individual patient. We went on to ask the question for stewardship of organs, how do these individuals perform when you compare them to kidney alone? And not unexpectedly, when you make the decision to allocate kidneys with livers, regardless of whether they had kidney failure or not, there is a poorer survival of the kidney over the first four to five years than if you gave it to a kidney recipient alone. So that was one of the trade-offs we realized that we were making when we developed the policy. And so just for the sake of the medical eligibility criteria, here is what the final policy ended up being, which was dialysis as defined by a 27-28 form, so chronic end-stage renal disease. A most recent EGFR at or below 30 mLs per minute when the individual has had a pre-existing diagnosis of chronic kidney disease for the antecedent 90 days. The acute kidney injury group was a combination of one or both of the following criteria for six weeks. We felt that the combination was important because in real life, a patient comes into the hospital, you try to manage their acute kidney injury medically, then you dialyze them, then you think they're getting better, but then you're wrong and you're dialyzing them again. So we thought that that was more representative of the clinical experience of the patient, and we decided on six weeks of dialysis or six weeks of EGFR, 25 or below, or six weeks of the combination of the two. And importantly, at the time, we vested the transplant nephrologist with being the individual responsible to make the call. So we removed that back and forth that could have turned out to be a contest of personalities. Okay, let's move on to the safety net. Now, one thing that was talked about was how many kidneys are actually occurring in that first year after transplant. And this graph shows things in percentages, and these are diagnoses entered at the time of the first liver transplant. This is not a perfect graph, but I've distilled it out for you in the statement at the below, which says that on balance, individuals are listed for a kidney if they've had a liver transplant six and a half years after the liver transplant. And only 19% of the kidney registrations that occurred in this eight-year window were actually in the first year after the liver transplant. So a very small percentage of individuals were listing in that first year after liver transplant. We then asked the question, if you were on dialysis, yes or no, did it make a difference? And again, the real take home message is at the bottom where only 7% of liver only recipients who received a subsequent kidney listing were on dialysis prior to the liver transplant. Now that's either because they received an SLK because they were on dialysis or they recovered kidney function, right? So I think that's another way to think about that. A conversation at the time was we were going to disincentivize live donation, live kidney donation to recipients of livers who needed transplants afterwards by having a safety net in place, right? So then the first question was, well, how many living donor transplants are actually occurring in this population? So this is the total number and I've made read the living donors. You get that flavor that it's somewhere between 35 and the low forties per year, and that's occurring at any time after the liver transplant. And then if you ask the question, how many of those living donor transplants were occurring in the first year, you see that we're averaging on balance about six living donor kidney transplants into liver recipients needing a kidney transplant in the first year following their liver transplant. So there was not a lot of live donation of kidneys in this population prior to the policy going into effect. We felt that this should address a patient need. I think one thing that Rio has always said that I agree with, and I know David practices, I'm not a kidney person, David's not a liver person, and Rio's not a liver person. We are individuals who take care of the end stage organ failure population. Those are kidney patients and liver patients, and we have to think about them as a group. So the first question we asked was, if you have a liver transplant and you're listed for a kidney, how do you fare on the wait list compared to the kidney transplant population alone? And in fact, you do poor, right? You do less well on the waiting list if you've had a liver transplant than if you are on a kidney transplant alone, this slide breaks it up into less than one year and more than one year. But I think we've proven that there's a reason for a safety net. These individuals don't do well on the waiting list. And then because we're all stewards of organs as well, we wanted to avoid doing futile transplants. And what this analysis shows that if you have a liver transplant and you're on the waiting list for less than three years, and you get a kidney transplant, you do as well as if you got a kidney transplant alone. So transplanting individuals with liver transplants who need kidneys earlier is both appropriate because they have a harder time on the wait list and they do as well with the organs as if they were kidney transplants alone. So this is just the safety net criteria. In the interest of time, I'm just going to let you read this, but the concept being you've got to go 60 days after the liver transplant to see if there's renal recovery and to see if you engraft your liver and do well. And then you have to recertify the need for the transplant every 30 days until three months, which would be the definition of end-stage renal disease. And that's the policy there. So what were some of the concerns about the SLK policy? There are many actually. So many people thought that even though we're calling these eligibility criteria, they'd be interpreted as guidelines and protocols. And therefore, there would be more listings for liver kidney transplant. We had a lot of debate over the ideal EGFR. I'm not sure we were 100% correct. I think the data is going to say we weren't wrong. The medical eligibility criteria for CKD and AKI could be gamed or could be abused. I think Rio's going to show us some data on that. We thought that there was concern that withholding the SLK could lead to increased waitlist mortality and post-transplant mortality. We're not going to talk about that per se in a formal manner here. We've got some slides, but I will tell you that there's a formal analysis in the forthcoming paper that I alluded to. Individuals felt that the 60-day wait could increase mortality and that a kidney from a different donor would have a worse immunologic outcome. And so I'm going to leave you all with this slide saying that when balancing between objectives like equity and utility, you're never going to make anyone happy. And I think that's a universal statement. So how did we do and how is the policy performing? And with that, I'm going to turn things over to Rio and let him bring you up to speed on where we are with the outcome of the policy. Good morning. Thanks, Rich, for a really comprehensive look at what we did before we implemented the policy and some of the justification. Just to emphasize that for every single policy change, major allocation change that UNOS makes, there's always a plan, 100% of the time, to monitor the effects of every large policy change, including looking at the policy at both intended and unintended consequences. And this gives us the opportunity, once equilibrium is reached, to really modify our policy if we need to. The primary goal of the SLK policy was, one, to make sure that we had good medical eligibility criteria for people who qualified for an SLK when there were none to begin with. So before this policy, anyone who was listed for liver didn't have to meet any criteria for GFR or anything else before they were listed for a SLK. And so a lot of the motivation was to actually establish these criteria when there were previously none. Two of the concerns was that the number of SLK transplants, if we were to incorporate these medical eligibility, would continue to escalate and, in fact, rise. Some of the folks in the kidney transplant world thought that the EGFR criteria were way too liberal for the patients with end-stage liver disease, despite the fact that we all know that creatinine-based estimates of EGFR discriminate a little bit against liver disease patients. The other thing is that the safety net, as Rich mentioned, really gives us the courage and the impetus to try to do liver transplants alone in warline patients. If your patient who's waiting for an SLK and actually qualifies for an SLK could potentially do with the liver alone, and you're just not sure, even if they meet medical criteria, the safety net is one thing that motivates us to perhaps do a liver transplant alone. And from the practical standpoint, this may be quite useful in highly sensitized patients. In any event, the safety net was made so that people who are on the edge of getting acute HRS, for example, and might recover their renal function, even though they might qualify for an SLK, this would give you the courage to do a liver transplant alone. And just parenthetically, some of our patients that were listed for SLK, for which we did liver alone, in fact recovered their renal function before we could list them for a kidney transplant, we're using the safety net. So what have we actually seen since the SLK policy in place over the last two years? And this is an important part of what the analysis is of the effects of the allocation policy. First of all, who is currently being listed for SLK? You can see that the great majority of patients, the overwhelming majority of SLK registrants have chronic kidney disease and non-sustaining AKI. This means that the criteria that are being used is overwhelmingly chronic kidney disease Thank you for your cooperation. And that very few of the patients being listed are using the sustained acute kidney injury, which begs the question, do we have appropriate AKI criteria? We can look at why most of the patients are being done under chronic kidney disease. It does probably imply that most of the people with quote unquote acute kidney injury or even just HRS have some degree of chronic kidney injury before they have their acute injury. Many of these quote unquote AKI patients may have acute on chronic injury, but there's an interesting that the great majority of the patients meeting eligibility are meeting it through the kidney chronic kidney disease criteria. One half of all SLK candidates in the CKD criteria are actually on dialysis, not just meeting it through the GFR requirements. So well over half or at least half. What about the transplant numbers of SLK transplants? Again, the fear was that if we didn't continue with the policy, we would continue to see a large escalation and a rapid increase in the transplant numbers. And what were the effects of the SLK policy on other populations? So contrary to all the anxiety that was given by some board members, there actually hasn't been a huge increase in SLK registrations by date following the implementation of policy. And in fact, the total number of SLK transplants that are being performed is actually remain now stable as opposed to this inexorable rise that we saw in the previous years before the SLK transplant. So despite the fact we're doing more and more liver transplants these days, the number of SLKs done has remained relatively stable after the implementation of the policy. And to that point, SLK transplants actually now represent a smaller percent of both total kidney and liver recipients. This is the percentage of the kidney recipients before and after the SLK policy. And again, slightly lower percentage of all kidney transplants are SLK, same with the liver transplants. So we're doing more liver transplants without a kidney percentage-wise after the policy. Pediatric patients have not been adversely affected in a significant way by implementing SLK policy and establishing medical criteria, but there is a fair amount of regional variation that exists in terms of how many transplants are done by the centers in different regions. Here you can see the percentage of SLK transplants pre and post in the various bars. So some areas went down, some went slightly up, and so there's been a regional variation between different regions in terms of the percentage of SLKs that are being performed. You can see both registrants and transplants by era as well. SLK registrants total and then pre and post liver transplants by region. What about overall patient and graft survival? In terms of the survival for SFK versus the C-Stone or kidney and liver and lung patients, you can see the green line is the pre-SLK transplants and the post-SLK transplants. You can see that basically that we have not seen a subsequent decrease in patient survival of patients getting SLK transplants pre and post policy implementation, and specifically there is no change in the survival of the kidney graft. That makes sense because the survival of the kidney graft is really dependent on the survival of the patient post-SLK, and also there has been no change in the liver allograft survival pre and post-SLK transplant policy. Now what about the safety net? Has the safety net performed as intended in terms of rescuing some of these patients that did not get an SLK? And you can see that post-SLK that as intended, the transplant rates for kidneys can be added to the waitlist within a year of receiving a liver transplant has gone up. That was obviously what the safety net was supposed to do. Increased access for those patients post-SLK that showed to have a decreased survival on the waitlist. And again, if you look at the distribution of days between the private liver transplant and kidney transplant post-SLK, there's a big spike in the first year after registration, which again was a point to prioritize those patients that underwent a liver transplant and are on the kidney waitlist. And importantly, the safety net appears to have decreased the waitlist mortality for the recipients of that same disease. Again, one of the intended consequences of creating the safety net. So overall, and this is obviously depends on one's perspective, the SLK has been a success as defined by whether we achieved the intended goals. So now post-policy, we actually have a slightly lower percentage of diseased donor kidneys that are going to the recipients. That is if you combine both SLK and the kidneys that are allocated under the kidney safety net as well. So from the nephrologist standpoint, we're not taking more kidneys out of circulation for the kidney-alone patients. The number of SLK transplants have remained stable. There hasn't been this inexorable rise or even acceleration of SLK transplants. We haven't been able to detect a deleterious effect on other populations, including kidney alone, pediatric kidney, or other kidney pancreas transplants. There's a slightly lower percentage of total diseased donor organ transplants, diseased donor kidneys going to liver transplants with renal failure. And that includes the sum of the kidneys going to the SLK patients and the kidney after liver transplant. Now, we do think there's more work to be done. Now, is it that the chronic criteria are too liberal or the acute kidney injury criteria too strict? Why is it that everybody is pretty much being listed under the chronic criteria? Or is it just the fact that all these patients that have sort of quote-unquote type 2 HRS or whatever actually have acute on chronic renal insufficiency? Should we consider any changes to the safety net criteria? Are too many kidneys being used this way? Is it too liberal? Is it too conservative? We need to see the utilization and continue to follow these outcomes. Now, as mentioned before, we absolutely need to hurry up and establish similar medical criteria specifically for heart, kidney, and lung kidney recipients, probably thinking about a safety net as well to motivate heart transplanters and lung transplanters to reform their thoracic operations alone and forego the kidney for borderline patients with a marginal rise in their creatinine. These are all things that need to be debated, but hopefully be implemented soon so we have a similar criteria and similar consistent behavior with these other multi-organ transplants as well as liver kidneys. Now, how do we actually put this into practice? And it all depends on your transplant center that's doing it. Who do we actually think can have a liver loan? Or when is it advantageous? For example, what about people that were broadly sensitized to have high titer class 2 enema? Should we think about just doing a liver loan on these patients? Otherwise, they may die waiting for that liver and kidney combination. We do want to think about maybe identifying those acute kidney injury patients that might do well with a liver and loan and use the safety net as a backup. And maybe we should be more aggressive around identifying liver donors up front. If we risk liver transplant alone, can we expect our patients to get our kidney alone? And which kidney recipients with cirrhosis can have a kidney alone? In other words, does every kidney recipient with portal hypertension need an SLK? These are all questions that could be answered at your center and otherwise. And finally, an SLK is certainly a little bit more of an operation than a SLK transplant. And so are they, in fact, a viable candidate for the combination loan? Should we just give them a liver loan and get them off the table? So these are individual decisions that are made in transplant centers. So I wanted to pause there and give opportunity for people on the Q&A box to go ahead and answer questions. So thank you very much for your time. Well, thank you, Rio and Rich and Mike. I think that was a really engaging discussion. And it's great to hear that follow up. I'm sure Rich recalls when we were really pushing to drive this pathway through. And I've got to say that I feel a lot of satisfaction that with Rio's help, we've been able to see a very successful movement in trying to get kidneys with livers into the right patients. And I'm really pleased to see, as you were pointing out, Rich, how effective it was in identifying the right patients to get the organs and enough patients to be able to get those safety net kidneys in a satisfactory time period to where they have the outcomes that we wanted to achieve. So I want to thank both of you for making that possible. What I wanted to go through is to answer some of the questions that we have in the chat box and also to start out kind of off of one of the questions that Rio posed and to either of you to make comments about where you think with broader sharing, the obstacles are that we go with assigning kidneys to livers. And do you see any impacts that we need to be aware of due to the changes in allocation that are going forward with what we've seen so far with SLK? Yeah. do you want to take that first? Yeah, I just wanted to say there are things that we need to think about because right now anyone within the 150 circle for liver gets the kidney allocated. But if you go beyond that, with a MELDA 29, you'll, I mean, up to 250, you have to have a MELDA 29 for you to get the liver allocated with the kidney and beyond that, up to 500, the opioid is not required to give you the kidney, and there are some sick patients being allocated the liver for a MELDA 40 that are not getting the kidney. So these are considerations. Are these rules effective now that AC is in place? Are these appropriate cutoffs? And what about the MELDA 40 patient that is just at 251 miles and not getting the kidney because it's not required to be allocated currently in the current policy? So I do think those are things that need to be addressed and thought about as we go forward and look at some of those patients that are not getting the offers for the SLK when they are outside of the 250. David, there's a historical precedent here, right? So when CAS went live in 14, it created a conflict between CAS and the share 35 that was the way livers were allocated. We had the same problem where allocating the kidney was based upon a collegial agreement, not mandated in policy. And we changed that in the policy, and I think to get to what Rio is addressing, this requires a policy update in the context of the larger changing approach to allocation of organs. But this should be very easily achievable. There should not be anything controversial about that fix because we've already done that fix in the past and it was accepted. Yeah. I appreciate that. So what about the HRS kidneys? I see there is a question from Nagin Murad about patients with HRS booked for a liver transplant. Can they automatically have SLK and have both transplanted? I think maybe reaffirming when we are automatically able to transplant a patient who meets and what time they meet the criteria might be helpful. And then the other question is, since HRS is a functional failure, can these kidneys be transplanted in other patients without cirrhosis? Well, I'm a little confused by the question, so I might be misinterpreting it. But the first half of the question, I would say that the diagnosis of HRS fits into probably the acute kidney injury pathway. And therefore, if you have HRS and meet the acute kidney injury criteria, then you could get an SLK. And similarly, if you had acute on chronic kidney disease, you had antecedent renal insufficiency and had HRS on top of that, you could then get it through the chronic kidney disease pathway. There's no specific hepato-renal syndrome pathway to allocate a kidney with a liver. The second question sounds like if an individual dies with liver disease and has hepato-renal syndrome, are those organs retrievable and then transplantable? I would really defer to you, David, or Rio, I don't do organ recovery. I don't know how frequently OPOs pursue patients with chronic liver disease or liver failure for the donation of other organs. I actually have never really thought about that, so I'll defer that to you. Yeah, I routinely take kidneys from patients with liver disease, and if they have renal insufficiency, I really think about the duration of which they've had that renal injury. But in terms of the first question, it is interesting that very few of the SLK units are being listed under the acute criteria, which really begs the question, why is that? And so I think we need to look into that a little bit more. I can tell you, again, I don't want to, stuff is embargoed. Amber has done some analysis on that. Your observation that very few, Rio, is actually very correct, I think it's 46 or something. I can tell you that survival of patients with AKI pre, liver, and post is not different than the rest of the population. So until there's more data, it doesn't look like those individuals are doing worse after transplant. Why is a different, the why that you asked is a different question. Yeah, and I do think that many of our patients with HRS or acute kidney injury don't start out with normal GFRs when we listen for SLK. And certainly calcineurin inhibitors play a role in that too, long term, which don't help in multi-organ transplant recipients either. I do think, David, that's a very good point, if I can chime in. I think people need to remember when we were, it's always hard when you're retelling the story to remember all the variables that were circulating at the time. But one of them was that we weren't necessarily, the goal was not to restore normal kidney function for the duration of the liver recipient's life. The goal was to provide adequate renal function or try to ensure adequate renal function for the first year post liver transplant, because that's where the morbidity and the mortality appeared to be. And we, there was the very appropriate, I think, conversation about being a good steward of organs, right? So if we're going to do a liver transplant and the patient's not going to live a year, that's a liver that could have been used in somebody else. So it's not surprising to me that if people, when they really start to dig into this data, it's going to look like kidney after liver transplants are going up dramatically. Because in fact they are, because you have more people living with liver disease or liver transplants longer and developing chronic kidney disease. The key thing for people to focus on are how many of those kidney after livers occurring through the safety net, right? That's the key variable because as the population increases, of course there's going to be more people listing for kidney, because as you said, there's more exposure to calcineurin inhibitors, there's more chronic kidney disease, patients are being listed, et cetera. So that's an important distinction to be made. And just to add, you have to have the renal criteria within the year post liver transplant to use the safety net. So it's not patients that are five years out on chronic calcineurin inhibitors that slowly and inexorably, like 30% of them are going to have renal insufficiency by that time. That's not who we're addressing with the safety net. The safety net is obviously people who get into renal trouble very early on, that is, i.e. one year post liver transplant, or stayed in renal failure at 60 days post liver alone, for example. And that's a great point, Rio, and I think you show the data that shows maybe the safety net kidneys have gotten up to about 70 per, I forgot what the timeframe was for that. When we did the analysis for the manuscript, it turns out that on balance, 4% fewer kidneys are being allocated to liver patients through both SLK and the safety net than were allocated to SLK prior to the policy going into effect. Getting to the point that you were making when we were talking off camera, which is it would have been great if we just slowed the rate of rise. In fact, we blunted it, we stabilized the rate of rise, and to me, that is a policy success that was a little bit unanticipated. Well, you know, and some of this conversation begets another question, and that is, what about the re-transplants when there's kidney disease in a liver recipient who requires a re-transplant, say, you know, more chronic or say a recurrent disease or develop other complications with the liver where they need a re-transplant in SLK? What do you think the modifications, if there would be any, would need to be considered in those patients? So David, are you asking for like a person who received a redo liver in the first year? Is that what you're sort of thinking about? Actually either case, but most, what I was envisioning is, say you have a patient that needs a re-transplant four years out. So they've been out, they've now developed chronic renal insufficiency, maybe even some AKI with their liver. How do we, would we consider the same factors that we consider in the first go round? Would you be more inclined to do a kidney with the liver on the re-transplant because of what's going on? What about that population? Well, I'll tell you, clinically I'm on service. We're both on service as we know, we were out this morning. I have an individual who is a redo of the liver who's qualifying for the SLK via the criteria that we have. I think the question you're asking is if you have a redo liver and you have native kidney function and perhaps they're not quite making the EGFR cutoff of say 30, should we loosen the criteria for that individual? Currently that would violate the policy because the policy wasn't written to account for that scenario. My own opinion is it probably falls into the same category as the first time through if you're looking at it from a kidney function perspective, but that's certainly a reasonable conversation for the community to have. No policy should stay in stone in perpetuity. It should be revised to modify the challenges we're facing at the time. So I don't know, Rio, do you have an opinion about that? Yeah, I don't see why a redo liver candidate should have any more priority than a primary liver kidney transplant candidate because both of them could need a kidney and I don't think you necessarily have to be more liberal with the redo transplant. I mean, actually for utility of organs, redo liver transplants are usually quite a bit more challenging, associated with more blood loss, and there may be reasons why you may want to wait to do your kidney transplant in the redo situation. So no, there's no reason a priori I would think that you'd give more priority or loosen up the criteria for a redo liver candidate than a primary liver kidney transplant candidate. I do think that we should, you know, really remember that I do think creatinine-based estimates of GFR, we should probably move beyond that at some point in modern medicine because there are so many faults to it, you know, including even using creatinine as part of the MELD score, which obviously disadvantages women and small men compared to large ones. So there's a lot that we can change, including the EGFR criteria, I think, that's my personal opinion. But when we get better measurements of EGFR than not creatinine-based, I think we can more accurately see what a cirrhotic, or end-stage liver disease patient has in terms of renal reserve compared to other patients. So I want to come back to something Rich had mentioned earlier a little bit about sort of judging things by organ utility and length of function of the organ. When we get into, and I think it's going to get very challenging when we get into heart and kidney and lung and kidney, where survival is very different than a lot of the, you know, in terms of long-term versus liver, then how are you really going to be able to judge the use of those organs in terms of life year extension or organ life years? Well, I'll take that first and I'll let Rio, because I think maybe he and I think differently on this, maybe not. I personally think that, you know, we do many kidney transplants that don't last the eight-year median time or 10 years that we would expect the deceased donor kidney to function. If as a community, we made a decision that a certain group of heart recipients were entitled to the kidney, acknowledging, as you say, Mike, their overall survival is going to be poorer. Therefore, the kidney survival is going to be poorer than if we put it into a kidney recipient. I think as long as we have a fair way to do it, so it's not capricious, and ideally, so in a world where we would also address which multi-organs come first and are there certain kidney alone individuals who should come ahead of multi-organs? I mean, if we went through as a community and answered those questions to our satisfaction, I'm comfortable with the fact that kidney might not last as long in a heart recipient as opposed to a kidney alone recipient. To frame it a different way, you know, we always balance or try to think about both utility and equity and try to, quote unquote, balance it. Now there's many policies that were put in place, including in kidney, that actually decrease utility but increase equity. For example, we prioritize very, very highly sensitized patients. Are they going to have the same overall graft survival as someone with a 0% PRA? No, but we thought that biologically, it's really unfair to not expose them to the best donors that they can. So admittedly, that may end up with a slight decrease in utility. Another example is that right now, we give more priority for patients that wait longer times on dialysis. So patients with eight to 10 years of dialysis get priority and they get more points, obviously, as they wait. We think that's fair because they got on the list a lot longer. Is that the best utility for those kidneys? We know that graft survival is poor in kidney transplant the longer you've been on dialysis. We already know that, but, you know, it seems unfair to deny them after a certain amount of time. It's like, oh yeah, you've waited too long because of our system. You're going to get lower priority because of utility of your kidney. Your kidney is not going to last as long because you've been on dialysis for 10 years. So that seems like an unfair thing. Do we penalize patients who have been on dialysis for 10 to 15 years? No, they've survived the gauntlet of being on our terrible wait list for so long. Does that mean we're going to maybe get decreased utility of that organ? Yes, it does mean that, but it doesn't seem fair for a patient who's lasted for 10 years to all of a sudden say, oh yeah, your kidney survival now, graft survival is now bad. So we're going to put you even further on down the list. And so I think you always have to justify a little bit utility of the organ with justice and equity. And so I think I actually echo Rich's thoughts that you have to really balance these things when you talk about policy. Because if you do something that only results in the best possible stewardship of that organ in like how many years you're going to get out of that organ, we wouldn't really be doing 70-year-olds. We wouldn't really be doing, you know, you'd be doing all the dialysis or at least the younger adults first once they've gotten over their sort of non-compliant age. But I think you have to be careful about looking at utility alone. That's my point. Yep. I agree. Well, we have one last question about a drug-induced liver injury patient. There's an example that was brought up on the chat box about a DILI patient who has preserved liver synthetic functions, but a BILI of 49 that gets AKI, creatinine goes from normal to 7.7, and is on dialysis without improvement in the renal parameters. What do you do with those patients? How do you proceed with a patient like that? Well, I'm going to let Rio take that first because of the liver components of it. Then I'll chime in about the kidney. If it's acute and it's drug-induced, they usually have fulminant acute liver failure and a status 1A, if that's really how you're going to transplant them to an acute setting. And in most cases, I would just assume that their kidney has some chance of recovery. I wouldn't really do a liver kidney alone unless you told me there's like no blood flow to the kidneys, there's acute corticonecrosis. There's zero chance of that kidney coming back. But most cases of ATN, unless they're out 30 to 60 days, which most of these drug-induced liver injuries, if they're that severe to require a liver transplant, they're either going to be acute or sub-fulminant. And so my initial take is, you know, you got to save this patient's life. Just do a liver alone and see what happens to their renal function. That's in general what I would do. Yeah. And I, so I would take, I was going to say the same thing. The lifesaving procedure there is the liver transplant. My clinical intuition would tell me they're most likely going to recover their renal function. And if they don't, that was kind of the original reason for the safety net. That patient would still qualify in the safety net pathway. And that's exactly why we put it in place because discussing the acute liver injury patients that made us say, well, wouldn't it be great if we had a safety net? And that's what started the whole safety net concept. Exactly. So if I guess wrong and their kidney function never recovers after 60, 90 days, I pop them on the safety net and hopefully they'll get their kidney transplant because I wasn't a good enough clinician to tell that the kidneys weren't going to come back. Yeah. And I think, and I thank the audience for that question because that's a perfect question to underscore exactly why this policy was created the way it was and, and how it's been effective thus far. So at this point in time, it's a perfect question to close us out. And I want to say a special thank you to the ASLD for hosting this conference and to Mike Shiltsky is chair of the liver intestinal and liver surgery SIG to Rich Formica and Rio Hirose, our speakers who worked so hard to put this policy together. And it'd be, it's, it's been a wonderful, very good dialogue that we've had and we appreciate the updates and thank you guys so much for your time and effort. And we look forward to that manuscript coming out. All right. Thanks guys.

Simultaneous Liver Kidney Transplant

SLK policy

American Association for the Study of Liver Disease

medical eligibility criteria

organ allocation

utility and equity

chronic kidney disease

acute kidney injury

safety net