 As Dick explained, we're working on this project that I spent three years convincing the United States government that they wanted to give me PHI, patient health information, and succeeded and we are contacting these individuals. And when we meet these people, as you might expect, they are some of the nicest people in the world. So these are people who donated a kidney and then went into kidney failure themselves. The one thing I can say just overall is that they are clearly generous people. They have no regrets. They're not angry and sometimes I feel like I'm the angriest one in the room. So what I want to talk about today is when altruism goes awry, when living kidney donors develop and say adrenal disease. I have no financial relationships to disclose and I won't discuss any off-label use. So it's estimated that there are over 150,000 living kidney donors in the US since 1954. Notice the word estimated because we actually didn't keep track for many, many decades. Since 1996, the Oregon Procurement and Transplant Network gives donors who develop end-state adrenal disease special priority for getting a deceased donor kidney. And as of May 31st of this year, over 430 candidates have received this special priority. So that's an underestimation because it only includes those donors who are listed for a deceased donor after 1996 and it only includes those who get listed. So those who develop end-state adrenal disease and decide to stay on dialysis, we don't know about them. And those who die even before they get on dialysis but with a GFR less than 20, again, we don't know about them. And interestingly, the dialysis, the USRDS database does not keep track of whether people have one or two kidneys or whether they were a former donor. And I've been in talks with them, trying to convince them that that might be a useful thing for them to collect and so far I have been failing miserably. So today the OPTN collects two years of follow-up data only. If you're going to develop kidney disease after you were a living donor, it's probably going to happen a lot longer than two years from now. So there's no long-term clinical or psychological data collected. So this former living donor project is that we're enrolling all former living donors who develop end-state adrenal disease. And as Dick mentioned, we got some personal health information from HRSA. We've also sent out a number of spam emails to every nephrologist and transplant surgeon whose email we can locate, asking them to help us find candidates. And in June of 2014, when the project I'm about to describe got started, we had 165 individuals consented. Today we have closer to 200, although we have about 175 blood samples. And one of the things we asked them was, could we contact you for other research that we might be interested as well as doing this genetic study? And most said yes. So we decided, I had two students I was working with that summer, Jackie Wang, who's a medical student here at Pritzker, and Mike Poulson, who's a medical student at Georgetown. We decided that we would like to talk to those donors who either develop kidney disease within 10 years of donating or those who didn't have health insurance at the time that they donated and how that might have impacted on whether they got appropriate follow-up care and then their subsequent kidney disease. And our aims were to explore the impact of donation and subsequent end-state renal disease on family dynamics and explore the patient's experience with the health care system and finances. And it's easier to see the methods this way. So we started with 165 going through our study. On the left-hand side, you can see that 28 developed end-state renal disease within 10 years of donating. We excluded individuals, we didn't want to talk to parents who donated to a child because we assumed that the answer was going to be what you see in the literature. It was my kid, what else was I going to do? So we decided to stick to only interviewing those who were first-degree relatives but not parents to child donors and we also, and so out of that 28, we had 24 potential subjects were contacted and we performed 12 interviews. One was actually a non-directed donor and we excluded him for the analysis. We had 26 who had no health insurance at the time of donation. 18 were contacted, 11 interviews were performed and we excluded two from analysis for this study because they donated in the early 1960s and that was before we had the renal disease act where renal disease becomes covered by health insurance, particularly being paid for by Medicare. And so they were interesting because both of these two people who were excluded talked about their donation as research and so we're including them in a different part of the project. But overall then we had 12 interviews of those who developed kidney disease within 10 years and we included 11 for the analysis and nine who had no health insurance. And our demographics is that 60% of our participants were African-American. It was 40% female, 60% male. A child donating to a parent was 15%. Most of our participants were siblings and this just gives you their age at interview, their level of education and the date of donation. So you can see that some of them donated in the 70s, 80s, and 90s and the fact that we know about them tells you that their kidney disease could have developed many, many years to decade after their donation. So after doing these interviews, they were about 60 to 90 minutes. They were tape recorded and then transcribed. We came up with actually about 20 coding categories but I'm going to talk about five of them for today. One was their decision making process. The second is what they understood about instructions for donor self-care after donation. The third is the lack of regret about having donated despite the adverse event. The fourth was advice for future donors and the donation process itself. And the fifth is the impact of the current project on their perceptions of their lived experience from donor to recipient. And as I quote these individuals, I'll be using male and female M&F and I for insurance issues and T for under 10 years of age. So the decision making process, there were two themes that came out very strongly. One was it wasn't really a decision, it was a spontaneous choice and the other was the rapidity of the process. So here are two quotes, I never lost no sleep over it. One man stated nonchalantly, I just said, well that's my brother, that's all. And a sister donating to a brother said I didn't think twice about doing it because I knew he needed it. And many actually also talked about how fast they thought the process went. Everything happened so quickly that it was, there was no time to think. When asked about instructions for donor self-care after donation, most responded they had been told simply to live a normal life, that one kidney is sufficient. They told me that you can live with one kidney, one woman explained. Well evidently you can live off of it, but you have to keep yourself healthy and nobody explained that to me. They told me go ahead and live your life like you always did. A few of the donors expressed a certain degree of self-blame then for their subsequent end-sadrenal disease, as one other woman lamented, I think I was just careless. When asked about self-care after donation, some blamed their subsequent kidney failure to bad luck or to God's plan. None explicitly stated that their donation was in part responsible for the development or even the timing of kidney failure. In fact one respondent though said that his wife wasn't so sure. She I know in the back of her mind still feels that maybe some people didn't basically do a thorough job on the medical side to fully look at my circumstances and maybe would have detected something which would have said hey, maybe you shouldn't do this because you've got some issues looming ahead. As I mentioned, despite the bad event, our population is different than any other study because every single one of them went into kidney failure. So one of the worst events, death is worse, but I would be interviewing them if they had died. So in a sense I caught the second worst, which is developing kidney disease themselves, but the interviewees were resoundingly positive about their original decision to donate. The decision I made to me was the right decision, stated one man. I never regretted it to a middle-aged woman. It was positive even when their kidney didn't last long in the recipient. So not only did some of them go into kidney failure within 10 years of donating, for some of them their kidney didn't even last for more than a few months in the recipient. It wasn't in the cards for my kidney to work for him, but we gave it a shot because it could have gone either way. It went the wrong way for us, but if need be, I would do it again. So again, just incredibly generous people, no regret. After developing end-stage renal disease, the original decision to donate was actually affirmed by all but one participant. So 19 of the 20 said, yeah, I would do it again. No questions asked. Saying things like if I had to do it over again, I would do the same thing. But this one participant said she would probably not have donated knowing that she would subsequently go into end-stage renal disease. But throughout, she expressed ambivalence and she isolated in her decision. So at one point, she conceded, I probably would have done it again, who knows. And then later in the same interview, she's ruminating, she says, had I known that I would be going through this, I don't know. I might have thought a little bit longer. Their advice for future donors was also an important thing. Most said they wouldn't change anything. I think they, the transplant community, did a good job and hopefully they can continue. But they did give three pieces of pointed advice. The first was that they all felt that the physician should have been more explicit about the risks. All the doctors, everyone said, oh, you're going to live the same. It's not going to be any problem to you and your kidneys. But if somebody at the time told me the risk, maybe you're going to end in renal failure. It's not like maybe I don't change the decision to donate, but I wish to at least know, at least one man's response. They also recommended to make sure that the transplant team informed the future donors that they have a strong community around them to rely on during and after recovery. So one man was very disappointed that after he donated and he and his brother were both in the hospital and then both went home, the family went to check on the recipient. But nobody bothered to check in on him because he was healthy, except for the fact that he now had this huge scar and really wasn't able to walk or cook for himself for the first few weeks. So he advised, make sure that the donors have a good support group around them, at least a couple of people that would drop in and see if they're OK. And the third piece of advice that we heard from several of our participants was that they need to be more acutely aware of their personal health after donation. I wish they wouldn't say to everyone, oh yeah, you're going to be OK, no problem, because it can be a big problem. The interesting thing, something we didn't expect was the impact of our project on their perception of their lived experience in donor recipient. One man just stated quite clearly that he would have never seriously considered any connection between his donation and later development of end-stage renal disease from lupus had you not called me and prompted me to think about it. That said, he and almost everyone else were still very positive about donation. So from our data, what I can say is that the most important finding is that despite this universal adverse outcome, our donors' recall of the donation experience is mainly positive. It mirrors the psychological finding in studies of living donors who don't have bad outcomes. So they have as positive an experience as those who donate, the more than 150,000 who donate and don't go into kidney failure. They felt that their decisions were spontaneous, so this gets into the whole issue of what we mean by informed consent. And despite that, looking back, they have no regret despite this outcome. They do recall the whole process, they felt it was rapid and didn't attend to any of the warnings from modifying behaviors to whatever extent they were disclosed. So what's important though, again, is that this is from a unique population, a population where every single one of them had a bad response. One of the things when we asked them, what would you recommend for the future, they said, don't tell donors that you're gonna be healthy, you're gonna be healthy, but at risk. Some respondents stated that their enrollment in the larger project, so the blood samples that we're collecting and the subsequent request to interview them made them more aware of the possible link between their donation and their long-term kidney problems. And so we were careful at that point to explain that it really can't be known in any particular case whether they would have built NSA adrenal disease even if they hadn't donated, unless the cause of their NSA adrenal disease was a unilateral traumatic injury to their remaining kidney. And we did actually have one like that, a woman who, because of some abdominal scarring, when she got pregnant, to uterus leaned on her other utera and caused that kidney to go into failure. But we also explained that one of the biggest risk factors to developing NSA adrenal disease is having a family history of NSA adrenal disease. And since this project only focused on those two family members, that again, it's not clear what relationship their donation actually had. It increased their risk, but whether there's any causality, we really couldn't tell them. There are limitations to our study, their population was quite heterogeneous from the time that he lapsed since their living kidney donation, which may influence the recall of events around donation. They were also a different stage of adapting to NSA adrenal disease. Some were on dialysis, others had already received a transplant, and some were pre-dialysis. All were first degree relatives, so whether there would be as much positivity and lack of regret in people who donated whether to friends or strangers, we don't have that data. And of course, there is a social reliability bias that they might be answering no regret because that's what they're expected to say. So it's been an interesting project. I've learned so much from the donors that have participated, and they've really taught me a lot. I wanna thank my collaborators. I've already mentioned Mike and Jackie, who are the students who did all the interviews. Megan and Colin were involved in both designing this study and then doing the coding analysis, as well as Jennifer Carlin. I wanna thank Sandy and Dick, who were involved in listening to us talk about what questions we were gonna ask. I wanna thank my funders, which were the McLean Center. We did get a small grant from the NIH for the blood study, even though they didn't fund this part of the project. The students were funded under U of C NIH summer training grant, and now Dick and I are being funded by the RWJ. So thank you very much, and I'll take any questions. My question is that September Williams from somewhere in California. My question is, is how long will it take for this information to get into the pipeline? I know of two donors right now, one of them African-American, one not. So I'm wondering how long it will take for this to be a part of the general transplant community. I'm sorry, what's this? Some donors going to kidney failure? Excuse me? I'm not sure what you mean by, well, this one. So right now, you know this. We have two presentations where there's suspicion of increased risk for donors. Right now in California, I know people who are being prepped to be donors. How long will it take for the doctors that are doing this with them and the transplant team to know this? So actually there've been two studies in the past three years, one from the United States and one from Europe, which started to look at retrospective data. And it's now, everyone sort of agrees that there's some increased risk of going into kidney failure if you were a living donor. We can disagree on how much of an increased risk, but there is at least consensus that there's an increased risk, whether it's bigger, small, and who the appropriate control group is, is being fought. But that's already in the literature. And the A-P-O-L-1 that Dick was talking about is being debated in the literature because all the data that we have to date is only on deceased donor kidneys and how they function in recipients. And so we actually don't know whether the same impact will happen with the living donor because it has much less problems with ischemia time and things of that sort. So that, there's a whole debate then. Do you sort of extrapolate or not? And since we don't know if our extrapolation from the deceased donor data are accurate. And so Dick and I believe we should be disclosing it with the caveat of disclosing it as uncertain, but others are arguing that until the data are certain, why are we just adding confusion to the pile? So I think we are getting it into the literature and into the conversations. Thanks. Thank you. Lainey, fascinating stuff. I wondered whether particularly you had any insight through the interviews into the number of patients who stated that they had no possible insight that this might be related to their, that the donation might be related to their failure. One possible explanation would be that they were ignorant and that could be a problem with consent that they weren't sufficiently educated. But another possibility might be that it's part of the self-justification to themselves that they have no regret. And I wondered whether you were able to get any of that out of the interviews. Thanks, Dan. I actually think there's a third explanation, which again is since the literature that's coming out about the risk of living donors going into kidney failure is really within the last five years, it's also possible that they weren't told because no one knew it. People suspected it. I mean, there have been some studies even as early as 2000, but nobody really had data proving that there was an increased risk of going into kidney failure. So I think that might be a bigger part in both of your other possible explanations. Going forward, what's gonna happen and whether people are gonna be talking about this more. But again, there's no way that they went, I mean, they have to meet with a nephrologist, a transplant surgeon, a living donor advocate. They were told the risks. They didn't hear the risks, so they didn't remember the risks and so how much they'll remember of this would be interesting to see as well and how carefully and clearly and repetitively people talked about the risks. I don't know because I wasn't there for that original conversation. All right, thank you very much. I wanna go on and into.