 Dr. Walter Glannon, professor at the University of Calgary. He's the author or editor of over 10 books. And today we'll be talking about are we underestimating the risks in living kidney donation? As Walter walks up, I'll tell you that Walter and I were the two different first year PhD students at Yale together. Walter was a tenured professor in Spanish literature who decided to change paths and go into medical ethics. I was a practicing pediatrician, and I'm not sure they knew what to do with either of us. So Walter, please join us. Thanks for the introduction. And thanks to Lanie and Mark for inviting me to speak. Eight years ago, I published a very short paper in the Journal of Medical Ethics. And it was a paper raising questions about risk, long-term risks, in living kidney donation. And like most philosophers, I didn't really spend a lot of time thinking about empirical issues. So there wasn't a lot of data in the article. It was motivated largely by a paper published by Julie Engelfinger in the New England Journal of Medicine, I believe, in 2005. And what struck me was she mentioned a couple of cases of healthy donor, people who were healthy when they donated, who subsequently developed end-stage renal disease and ended up on dialysis in the transplant waiting list. So that made me wonder about risk. So the paper really just raised questions out getting much into discussion about the permissibility, ethical permissibility of living kidney donation. About a year after the article came out, I got an email from a woman who said that her 23-year-old son was considering donating a kidney to a friend who was in kidney failure. And she asked me for my advice. And I said, well, you've got the wrong person. First of all, I'm not a nephrologist. I'm not even a physician. I'm a philosopher. And what you should do is speak with your general practitioner and a number of nephrologists to get a better sense of things. I didn't say anything beyond that. Apart from the fact that I was not an expert and that she was concerned about her son, I wasn't concerned so much about the informational aspect of this 23-year-old's autonomy, but whether to what extent his mother might be influencing his decision. But I just left it at that. I don't know what happened. I don't know whether he donated or didn't. But what I wonder now is whether with the additional information that's available, the data that's available, whether that would have influenced him in a way that would have resulted in a different decision, regardless of given the fact that I don't know what that decision was. But there is more data, and it will be interesting to see, would be interesting to see how this is going to influence the way people process the information about risk when they're considering donating. In a recent issue of JAMA surgery, this is earlier this year, 68% of slightly more than 1,000 respondents said that they would be willing to donate a kidney. Can you hear me? 21 in urgent need of the organ. 23% said that they would donate to select recipients. 9% said that they would be unwilling to donate. Roughly 60% said that monetary compensation of $50,000 would make them even more likely to donate, though 32% indicated that monetary incentives would not affect their desire to donate. I put these questions to some of my students in my bioethics course, and one of them said, provided that the $50,000 is USD and not Canadian. OK, so the survey raises a number of questions. Among them are the following. If prospective donors knew of the long-term risk, and I'm not just talking about perioperative risk, which I think a lot of people, at least initially, that's what they think of disease and their remaining kidney, would they be so willing to give one up? Would transplant organizations and physicians be telling those who express an interest in donating a kidney about the risk? So this is assuming that the potential prospective donor initiates the conversation with a physician. OK, it's a general practitioner, family doctor, whoever. So I'm assuming in these cases it's the individual who raises the question first. So recent publications, what the data show, cumulative incidence of end-stage renal disease in kidney donors is about 3 per 1,000 at 15 years post-donation. Even with an immediate reduction of GFR from nephrectomy at donation, studies suggest that the risk of developing end-stage renal disease from living kidney donation is not significantly higher than the risk for the general population. This is just two of the recent publications on the data about risk. But end-stage renal disease takes decades to evolve. There's a honeymoon period. This is the term that's used by Bob Steiner, who's a transplant nephrologist, and I'm going to be referring to some of his work. There's a honeymoon period immediately after donation because healthy donors, by definition, start out with normal kidney function. Kidney disease typically takes 20 to 30 years to develop in the general population. It may take even longer to develop in healthy donors. The standard 15-year period of monitoring function of the remaining kidney may not be long enough to provide an accurate measure of risk. So the question is whether the 10 to 15-year period is long enough. And recent studies, Steiner studies in particular, suggest that they may not be. So I'm referring to some of Bob Steiner's work here. One third of living kidney donors in the UNOS registry are under 35. So I'm thinking of this woman who wrote some of the email and thinking about her 23-year-old son when this comes up. Recent analysis suggests that for a healthy 25-year-old with no detectable medical conditions at donation, there may be an 8 to 11-fold increase of relative risk of developing end-stage renal disease from donation by the time he or she reaches 80. So it's important to distinguish between the relative risk due to loss of GFR at an effectiveness and absolute risk through the probability of diabetes and other kidney-affecting diseases. There's an issue of fairness here depending on how you interpret the data. And depending on how you think of the human lifespan and whether different stages of life have more value or whether you just consider the value of the life as a whole. Older individuals in the 50- to 60-year range may be excluded from donation if they already have or show signs of diabetes or hypertension. These are exclusionary factors. Younger individuals with no signs of kidney-affecting disease may be exposed to long-term risk by donating and reducing GFR. They would be considered better candidates. What would have been a fairly common mild kidney disease in the lifetime of a person with two kidneys may become, and I underscore may, become end-stage renal disease in the lifetime of a person with one kidney. Transplant recipients, so there's the benefit-harm ratio. So generally, the belief that the assumption is that the recipient obviously benefits from survival and improved quality of life. And the donor benefits psychologically from the idea that they save someone life or improve the quality of someone else's life. So the transplant recipient benefits physiologically and psychologically from survival and improved quality of life. And the donor benefits psychologically from the action and outcome. So it's a win-win situation. The overall benefit clearly outweighs the risk. But if the donor develops end-stage renal disease as a consequence of reduced GFR and chronic kidney disease later in life, so this is beyond that 15-year period, then the overall combined benefit to recipient and donor may be less than what many believe. Some would still donate knowing the real risk. So for example, an intrafamilial organ donation, a sibling may donate to a sibling parent to a child in spite of the risk, because there's something about the emotional relationship and the obligations that they may entail. So the dynamics are very different intrafamilially and that may influence not only the way a potential donor perceives risk, but also in terms of how risk may be a factor in the permissibility or the justification for allowing the donation. This does not diminish the physician's obligation to inform prospective donors not only of the 15-year but also the lifetime risk of end-stage renal disease. So a quote from Bob Steiner here. He says, we cannot tell some candidates that their lifetime risks are minimal and we have good reason to believe that they could easily be 10% or greater. We also cannot say that we have no idea of risk when in fact, we know a great deal about risk and we would not be protecting the donor if we allow donation with no idea of risk. Among other things, this raises questions about what counts as reasonable or undue risk. This is not to minimize the importance of autonomy. So reasonable risk, there's considerable ambiguity in the way one interprets these terms and it would be paternalistic to say, to deny the opportunity of an individual to donate because there was some risk. It's going to depend on the degree of risk and what goes on in the dialogue between the physician and the potential donor. If physicians are unsure about the risk based on available data, then the default position should be to discourage donation. Now, this is Bob Steiner's position. I think that's a little too strong. I would say at least not encourage it. Physicians have a primary professional ethical obligation to protect their patients. I call this primary beneficence and non-maleficence. They have a secondary professional ethical obligation to promote organ donation for transplantation. I call this secondary beneficence and non-maleficence. I would put this under the bioethical principle of justice. And the first, well, I mean, I call it beneficence and non-maleficence, but to me they fall broadly under the umbrella of justice. What about the idea of a uniform risk standard? Steiner says, to achieve a defensible uniform risk standard, we have only two choices. To minimize risk by accepting only completely normal, non-black, older donors with high normal GFRs, or to endorse a somewhat liberalized risk threshold, which would mean declining many acceptable young black and or low GFR donors and accepting many older candidates with medical abnormalities. What are some alternatives? Well, as everyone knows, prevent or reduce the incidence of end-states renal disease in the general population, but it's difficult to control processes, all the different processes, through which genetic, physiological, and environmental factors contribute to kidney disease. Regenerative medicine to repair replaced failed kidneys is highly desirable, but this is still quite a very early stage, very investigational, experimental, regenerative research. So, in conclusion, healthcare professionals, transplant organizations, primary care physicians, nephrologists, transplant surgeons have a duty to acknowledge what the effects of unilateral nephrectomy on GFR and the remaining kidney imply for the lifetime risk of end-stage renal disease. They must fully inform prospective kidney donors younger and older of this risk and discharging their duty to respect donors' autonomy and protect them from preventable harm. So, the key point here is to present all the information about risk. Again, respecting autonomy involves presenting all the available information. It's still without unduly influencing the decision of the donor or the potential donor. And even though there is no acknowledgement slide here, I wanna thank Laney and Bob Steiner for discussing these issues with me. Thank you.