Showing posts with label transplantation. Show all posts
Showing posts with label transplantation. Show all posts

Monday, March 11, 2024

Global disparities in kidney disease and care

 Here's a report on the availability of treatment of kidney disease around the world.  If you are unlucky enough to have kidney failure (which is a top 10 cause of death), it's good to be in North America or Western Europe. Most countries (70%) have at least a minimal capacity to perform transplants. But if I read the map correctly, preemptive kidney transplants (i.e. transplants before dialysis, in map D below) are relatively common only in the U.S., Britain, and Norway. (And worldwide, a transplant costs less than two years of dialysis...)

Bello, A.K., Okpechi, I.G., Levin, A., Ye, F., Damster, S., Arruebo, S., Donner, J.A., Caskey, F.J., Cho, Y., Davids, M.R. and Davison, S.N., 2024. An update on the global disparities in kidney disease burden and care across world countries and regions. The Lancet Global Health, 12(3), pp.e382-e395.

"Background

"Since 2015, the International Society of Nephrology (ISN) Global Kidney Health Atlas (ISN-GKHA) has spearheaded multinational efforts to understand the status and capacity of countries to provide optimal kidney care, particularly in low-resource settings. In this iteration of the ISN-GKHA, we sought to extend previous findings by assessing availability, accessibility, quality, and affordability of medicines, kidney replacement therapy (KRT), and conservative kidney management (CKM).

...

"Findings

The literature review used information on prevalence of chronic kidney disease from 161 countries. The global median prevalence of chronic kidney disease was 9·5% (IQR 5·9–11·7) with the highest prevalence in Eastern and Central Europe (12·8%, 11·9–14·1). For the survey analysis, responses received covered 167 (87%) of 191 countries, representing 97·4% (7·700 billion of 7·903 billion) of the world population. Chronic haemodialysis was available in 162 (98%) of 165 countries, chronic peritoneal dialysis in 130 (79%), and kidney transplantation in 116 (70%). However, 121 (74%) of 164 countries were able to provide KRT to more than 50% of people with kidney failure. Children did not have access to haemodialysis in 12 (19%) of 62 countries, peritoneal dialysis in three (6%) countries, or kidney transplantation in three (6%) countries. CKM (non-dialysis management of people with kidney failure chosen through shared decision making) was available in 87 (53%) of 165 countries. The annual median costs of KRT were: US$19 380 per person for haemodialysis, $18 959 for peritoneal dialysis, and $26 903 for the first year of kidney transplantation. Overall, 74 (45%) of 166 countries allocated public funding to provide free haemodialysis at the point of delivery; use of this funding scheme increased with country income level. The median global prevalence of nephrologists was 11·8 per million population (IQR 1·8–24·8) with an 80-fold difference between low-income and high-income countries. Differing degrees of health workforce shortages were reported across regions and country income levels. A quarter of countries had a national chronic kidney disease-specific strategy (41 [25%] of 162) and chronic kidney disease was recognised as a health priority in 78 (48%) of 162 countries.



Figure 3 Worldwide incidence of general, deceased-donor, living-donor, and pre-emptive kidney transplantations (cases pmp per year) (A) Incidence of kidney transplantation. (B) Incidence of deceased-donor kidney transplantation. (C) Incidence of living-donor kidney transplantation. (D) Incidence of pre-emptive kidney transplantation. pmp=per million population

Even in the U.S., we aren't able to supply enough transplantable kidneys for everyone who needs one. Domestic kidney exchange helps fill some of the gap, but the gap, and the resulting number of premature deaths, is still huge.  It's enough to make you think about global kidney exchange...

Friday, March 8, 2024

Dr. Guy Alexandre (1934-2024), gave birth to brain death in deceased organ transplantation

 The father of brain death has died.

Here's the NYT obit.

Guy Alexandre, Transplant Surgeon Who Redefined Death, Dies at 89. His willingness to remove kidneys from brain-dead patients increased the organs’ viability while challenging the line between living and dead.  By Clay Risen

"Guy Alexandre, a Belgian transplant surgeon who in the 1960s risked professional censure by removing kidneys from brain-dead patients whose hearts were still beating — a procedure that greatly improved organ viability while challenging the medical definition of death itself — died on Feb. 14 at his home in Brussels. He was 89.

...

"Dr. Alexandre was just 29 and fresh off a yearlong fellowship at Harvard Medical School when, in June 1963, a young patient was wheeled into the hospital where he worked in Louvain, Belgium. She had sustained a traumatic head injury in a traffic accident, and despite extensive neurosurgery, doctors pronounced her brain dead, though her heart continued to beat.

"He knew that in another part of the hospital, a patient was suffering from renal failure. He had assisted on kidney transplants at Harvard, and he understood that the organs began to lose viability soon after the heart stops beating.

"Dr. Alexandre pulled the chief surgeon, Jean Morelle, aside and made his case. Brain death, he said, is death. Machines can keep a heart beating for a long time with no hope of reviving a patient. His argument went against centuries of assumptions about the line between life and death, but Dr. Morelle was persuaded.

...

"Over the next two years, Dr. Alexandre and Dr. Morelle quietly performed several more kidney transplants using the same procedure. Finally, at a medical conference in London in 1965, Dr. Alexandre announced what he had been doing.

...

"In 1968, the Harvard Ad Hoc Committee, a group of medical experts, largely adopted Dr. Alexandre’s criteria when it declared that an irreversible coma should be understood as the equivalent of death, whether the heart continues to beat or not.

"Today, Dr. Alexandre’s perspective is widely shared in the medical community, and removing organs from brain-dead patients has become an accepted practice.

“The greatness of Alexandre’s insight was that he was able to see the insignificance of the beating heart,” Robert Berman, an organ-donation activist and journalist, wrote in Tablet magazine in 2019.

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And here's the story from Tablet magazine, interesting in a number of respects:

The Man Who Remade Death. Guy Alexandre was the first surgeon to remove organs from a patient with a beating heart. His colleagues thought him a murderer; Alexandre disagreed and revolutionized our understanding of death.  BY ROBBY BERMAN, Feb 4, 2019

"I met Alexandre a few months ago in his home in an upscale suburb of Brussels. The octogenarian is charming, affable and avuncular but he does not mince words: The physicians who accused him of murder “were hypocrites. They viewed their brain dead patients as alive yet they had no qualms about turning off the ventilator to get the heart to stop beating before they removed kidneys. In addition to ‘killing’ the patient, they were giving the recipients damaged kidneys that suffered ischemia … oxygen deprivation. The kidneys did not work well; they did not last long.”

"Given that brain death was not well known by the public in 1963, I asked Alexandre how he succeeded in getting consent from families to donate the organs. “It was simple. I didn’t ask. I told the families the situation was grim and I removed the organs in the middle of the night. When the family returned the next morning I told them their loved one had died during the night.”

"In 1961, Alexandre was in his third year of surgical training. He left Brussels for Boston to attend Harvard Medical School where he studied under professor Joseph Murray, the surgeon famous for performing the first successful kidney transplant between twins in 1954. After Alexandre successfully executed a number of kidney transplants between dogs in the laboratory, he was invited by Murray to join him in the operating room to operate on humans. It was there that Alexandre noticed a curious phenomenon.

"Murray turned off the ventilator in order to cause the heart to stop beating and only then did he extract the organs. Alexandre felt there was no need to damage the kidneys by depriving them of oxygen. He believed when looking at a human body with a dead brain that he was looking at a corpse that was suffering from a bizarre medical condition: a beating heart. In other words, the organism was dead but the organs remained alive."
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Earlier:

Friday, January 18, 2019


Thursday, March 7, 2024

Increasing kidney transplants by reducing discards of risky kidneys

 Kidneys from deceased donors are too often discarded. Dr. Joshua Mezrich, a transplant surgeon at U. Wisconsin, writes in Stat about how to reduce the rate at which high risk kidneys are discarded (after being on ice for a long time while being rejected by many patients). He proposes that kidneys that can be identified as high risk even before being recovered from the deceased donor  be offered promptly to patients/transplant centers that have indicated a willingness to take them. It would require transplant centers to keep current blood tests available for patients who are candidates for high risk kidneys (who may be candidates in part because they are far from the front of the waiting list...)

Too many donor organs go to waste. Here’s how to get them into the patients who need them  By Joshua Mezrich, Stat, March 2, 2024 

"So here is the fix. High-risk kidneys should immediately be offered to transplant centers that opt into a high-risk program as an open offer to their wait list rather than to a specific patient, on a rotating schedule with weight put on proximity to the donor hospital. Ideally the offer should be made prior to procurement of the organ, with final acceptance once it is removed and anatomy and biopsy results can be reviewed by the accepting surgeon.

"If the biopsies show significant disease and the function of the kidney would be inadequate for a recipient, the receiving center can request both kidneys for a single patient, termed a dual transplant (which has been shown to have good outcomes). If a center accepts a kidney, it can then choose the patient who will benefit the most from the transplant and has a long predicted wait time for a low-risk transplant, with informed consent. That would entail a discussion with the patient about expectations regarding the quality of the kidney, how long and how well it might work, and how much longer they might need to wait for a lower-risk kidney. The ability to match the kidney to a recipient is important, as high-risk kidneys need to go into patients who can tolerate the slow initial function. Centers that opt into the high-risk program will need to maintain an updated list of informed patients who are predicted to benefit from these kidneys, who can be called in as soon an offer becomes available. For them, taking a chance beats remaining on dialysis.

Friday, February 23, 2024

Directed and semi-directed living donation of kidneys: a current debate in Israel and elsewhere

 Israel leads the world in per capita living kidney donation. A good part of that comes from the work of Matnat Chaim (gift of life), an organization of religious Jews, who donate kidneys to people they don't know.  They are "semi-directed" rather than non-directed donors, in that the organization allows them to indicate some criteria they would like their recipients to have.  Sometimes they want their recipients to be fellow Jews, and this has generated some controversy in Israel.

Below is a study of this phenomenon, and in an accompanying editorial, a criticism of it.

Nesher, Eviatar, Rachel Michowiz, and Hagai Boas. "Semidirected Living Donors in Israel: Sociodemographic Profile, Religiosity, and Social Tolerance." American Journal of Transplantation (in press).

Abstract: Living kidney donations in Israel come from 2 sources: family members and individuals who volunteer to donate their kidney to patients with whom they do not have personal acquaintance. We refer to the first group as directed living donors (DLDs) and the second as semidirected living donors (SDLDs). The incidence of SDLD in Israel is ∼60%, the highest in the world. We introduce results of a survey among 749 living donors (349 SDLDs and 400 DLDs). Our data illustrate the sociodemographic profile of the 2 groups and their answers to a series of questions regarding spirituality and social tolerance. We find SDLDs to be sectorial: they are mainly married middle-class religious men who reside in small communities. However, we found no significant difference between SDLDs and DLDs in their social tolerance. Both groups ranked high and expressed tolerance toward different social groups. Semidirected living donation enables donors to express general preferences as to the sociodemographic features of their respected recipients. This stirs a heated debate on the ethics of semidirected living donation. Our study discloses a comprehensive picture of the profile and attitudes of SDLDs in Israel, which adds valuable data to the ongoing debate on the legitimacy of semidirected living donation.


Danovitch, Gabriel. "Living organ donation in polarized societies." American Journal of Transplantation, (Editorial, in press).

"Nesher et al are to be congratulated for reporting on a unique, effective, yet ethically problematic manifestation of living kidney donation in Israel. To summarize, living kidney donation has become “de riguer,” a “mitzvah” (a religiously motivated good deed) among a population of mainly orthodox Jewish men living in religiously homogenous settlements. According to the authors, the donors view themselves as donating altruistically within a larger family. The donations, over 1300 of them, 60% of all living donations in the country, have changed the face of Israeli transplantation, reduced the waiting time for all transplant candidates on the deceased donor waiting list,2 and minimized the temptation of Israeli transplant candidates to engage in “transplant tourism,” a phenomenon that was an unfortunate feature of Israeli transplantation before the passage of the Israeli Transplant Act of 2008 that criminalized organ trading.3

So, what’s the problem? Matnat Chaim (“life-giving”), the organization that facilitates the donations, permits the donors to pick and choose among a list of potential recipients using criteria that according to its own website,4 and as Nesher et al note,1 are not transparent. ... frequently the donors elect to donate to other Jews.  ... " Israel is a country with an 80% Jewish majority; a decision to only donate to other Jews, thereby excluding non-Jews, is a practice that, were it reversed in a Jewish minority country, would likely be labeled antisemitic. Concern that the process encourages racist and nationalistic ideation has been raised in the past6 and only emphasized by the public pronouncement of some media-savvy kidney donors.7

"What lessons does the Israeli experience hold for the US and other countries, faced as all are, with a shortage of organs for transplant? Conditional living donation exists to a limited extent in the US: DOVE is an organization that works to direct living kidney donation to US army veterans9; Renewal is an organization that encourages and facilitates living donation from Jews to other Jews but also to non-Jews10; in the 1990s an organization called “Jesus Christians” made organ donation one of its precepts.11 But in each of these cases, it is a minority group whose interests are being promoted.

...

"What now for Matnat Chaim? Given its prominent impact on Israeli transplantation, its allocation policies must be transparent and subject to public comment. Criteria must be medical in nature and religious or political considerations excluded. Fears that as a result living kidney donation rates will plummet are likely exaggerated. "

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I can't help reading this discussion while being very aware that Dr. Danovitch is an ardent opponent of compensating kidney donors, for fear that inappropriate transplants would take place if that were allowed.  In much of that discussion, inappropriateness of transplants focuses on possible harm to the (paid) donors, but the donors in the Israeli case are unpaid. Here his concern is that donor autonomy about to whom to give a kidney comes at the expense of physician autonomy in choosing who should receive a transplant, by "medical" criteria. But frequently those criteria have a big component based on waiting time, rather than any special medical considerations. So maybe in general he thinks that privileging the physician's role in this way is worth having fewer organs and consequently more deaths.

Still, I think he has a point about how we perceive what is repugnant. Having minority donors donate to fellow minority recipients seems much less repugnant than having majority donors specify that they aren't interested in donating to minority recipients.

But, speaking of donor autonomy, I'm not sure that there are practical ways around it, since semi-directed donors could always present as fully directed donors to a particular person that some organization had helped them find. So, we may just have to live with the increase in donations and lives saved that donor autonomy can support.

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Earlier posts:

Thursday, July 27, 2023

Kidney brouhaha in Israel: is a good deed still good when performed by a shmuck?


I ended that post with this:

"I'll give the last word to a Haaretz op-ed, also in English:


Monday, July 31, 2023

Altruistic kidney donors in Israel


...
and, here in the U.S.:

Friday, March 12, 2021

Kidneys for Communities

" A new organization, Kidneys for Communities, plans to advocate for living kidney donation by seeking donors who identify with a particular community.  Their come-on is "Put your kidney where your heart is.  Share your spare with someone in your community"

Tuesday, February 20, 2024

Frozen embryos are children: Alabama Supreme Court ruling

 The Washington Post has the story, which emphasizes the implications this ruling could have on in-vitro fertilization (IVF).  That would also impact surrogacy, and possibly deceased donor transplantation (depending on how it impacts the definitions of who is alive and who isn't...) 

Frozen embryos are children, Ala. high court says in unprecedented ruling. By Dan Rosenzweig-Ziff, February 19, 2024 

"The Alabama Supreme Court ruled Friday that frozen embryos are people and someone can be held liable for destroying them, a decision that reproductive rights advocates say could imperil in vitro fertilization (IVF) and affect the hundreds of thousands of patients who depend on treatments like it each year.

"The first-of-its-kind ruling comes as at least 11 states have broadly defined personhood as beginning at fertilization in their state laws, according to reproductive rights group Pregnancy Justice, and states nationwide mull additional abortion and reproductive restrictions, elevating the issue ahead of the 2024 elections. Federally, the U.S. Supreme Court will decide this term whether to limit access to an abortion drug, the first time the high court will rule on the subject since it overturned Roe v. Wade in 2022.

"The Alabama case focused on whether a patient who mistakenly dropped and destroyed other couples’ frozen embryos could be held liable in a wrongful-death lawsuit. The court ruled the patient could, writing that it had long held that “unborn children are ‘children’” and that that was also true for frozen embryos, affording the fertilized eggs the same protection as babies under the Wrongful Death of a Minor Act.

...

"The push for defining personhood has even affected tax law: Georgia now recognizes an “unborn child” as a dependent after six weeks of pregnancy.

Monday, February 19, 2024

Kidney exchange in the U.S. from 2006-2021

 Here's an interesting look at the (ongoing) development of kidney exchange in the U.S

Temporal trends in kidney paired donation in the United States: 2006-2021 UNOS/OPTN database analysis, by Neetika Garg, Carrie Thiessen, Peter P. Reese, Matthew Cooper, Ruthanne Leishman, John Friedewald, Asif A. Sharfuddin, Angie G. Nishio Lucar, Darshana M. Dadhania, Vineeta Kumar, Amy D. Waterman, and Didier A. Mandelbrot, American Journal of Transplantation,  24, 1, P46-56, JANUARY 2024.

Abstract: Kidney paired donation (KPD) is a major innovation that is changing the landscape of kidney transplantation in the United States. We used the 2006-2021 United Network for Organ Sharing data to examine trends over time. KPD is increasing, with 1 in 5 living donor kidney transplants (LDKTs) in 2021 facilitated by KPD. The proportion of LDKT performed via KPD was comparable for non-Whites and Whites. An increasing proportion of KPD transplants are going to non-Whites. End-chain recipients are not identified in the database. To what extent these trends reflect how end-chain kidneys are allocated, as opposed to increase in living donation among minorities, remains unclear. Half the LDKT in 2021 in sensitized (panel reactive antibody ≥ 80%) and highly sensitized (panel reactive antibody ≥ 98%) groups occurred via KPD. Yet, the proportion of KPD transplants performed in sensitized recipients has declined since 2013, likely due to changes in the deceased donor allocation policies and newer KPD strategies such as compatible KPD. In 2021, 40% of the programs reported not performing any KPD transplants. Our study highlights the need for understanding barriers to pursuing and expanding KPD at the center level and the need for more detailed and accurate data collection at the national level.

"Kidney paired donation (KPD) is rapidly evolving and reshaping the landscape of living donor kidney transplantation (LDKT). Since the initial KPD transplants performed in the United States in 1999,1 the scope of KPD has expanded substantially. With the inclusion of nondirected donor,2 it has progressed from simple 2-way or multiple-way exchanges to nonsimultaneous kidney donor chains3 and, more recently, to advanced and voucher donations.4 Downstream from nondirected donors, chains often conclude with end-chain kidneys allocated to candidates on the deceased kidney donor waitlist without a living donor (LD).5 Historically used to overcome the barrier of ABO/human leukocyte antigens (HLA) incompatibility, KPD is being increasingly used by compatible donor-recipient pairs to obtain more suitable kidneys for the respective recipients.6 KPD programs can be single center or internal, regional, or national.7,8 The largest multicenter or national KPD programs in the United States are the National Kidney Registry,9 the Alliance for Paired Donation,10 the MatchGrid/Medsleuth program,11 and the program operated by the Organ Procurement and Transplantation Network (OPTN).12 While multicenter KPD often expands the pool of candidates to improve match possibilities, there are examples of very successful single-center programs."

Sunday, January 28, 2024

Experiments for organ allocation (an idea whose time may be coming)

 Experiments to improve how deceased donor organs are allocated to waiting patients seem like a good idea...

OPTN Task Force sets goal of achieving 60K transplants by 2026Jan 26, 2024 

“we need to move quicker, be more responsive, and deliver results for the patients we serve,” said Dianne LaPointe Rudow, DNP, president of the OPTN Board of Directors. “The reality is that while the number of transplants continues to grow, so does the non-use of available organs and allocations of organs out of the intended sequence of offers.

...

"The need is clear. In the case of kidneys, the most transplanted organ, the number of kidneys recovered from deceased donors increased by 56 percent between 2018 to 2023. Yet the number of kidney transplants only increased by 44 percent, meaning that approximately one quarter of kidneys recovered were not transplanted.

...

"Under a proposed variance for expedited placement, currently out for public comment, the task force intends to develop a series of rapid, small-scale tests of innovative organ placement approaches and assess their outcomes to evaluate whether they could be incorporated into future OPTN policies. The task force also has committed to prioritizing studies that evaluate potential frameworks for allocating hard-to-place organs to increase the number of transplants and lower non-use rates."

Monday, January 22, 2024

Reporting and misreporting from Organ Procurement Organizations (OPOs)

 Because there are shortages of organs for transplant, it is important to measure how successful Organ Procurement Organizations (OPOs) are at recovering and transplanting organs.  But sometimes definitions can get in the way, and this was the case in islet transplants from deceased donors, into patients with diabetes.  Pancreatic islets are the cells that produce insulin, and it was (and I think still is) regarded as an experimental procedure to transplant islets from a deceased donor's pancreas, rather than the whole pancreas.  So islet transplantation was classified as a research activity.

To encourage this use of deceased donor pancreases, recovery of a pancreas "for research" was counted as a transplant. But some OPO's have heavily gamed this, reporting that they recovered a pancreas when the "research" wasn't connected to transplantation.  That loophole is now being closed.

Here's a January 18 memo from HHS, CMS, Center for Clinical Standards and Quality

Organ Procurement Organization (OPO) Conditions for Coverage – Definition Clarification 



"Background:

"The OPO CfCs are intended to drive improvements in organ procurement and transplantation through, among other provisions, the donor and transplantation outcome measures. OPOs are required to report data related to pancreata procured for research, and this data is incorporated into calculations used to assess compliance with the donor and transplant outcome measures and are used for re-certification purposes. To facilitate accurate reporting of data related to pancreata donors, the term “donor” is defined in CMS regulation to specify that, among other requirements, an individual would be considered a donor even if only the pancreas is procured and is used for research or islet cell transplantation.

"CMS has noted a significant increase in the number of pancreata procured since this definitionwas revised in 2020, raising questions about the interpretation of this definition by OPOs and how this definition is applied to reporting data related to donors of pancreata used for islet cell research. There is a concern that the increase in pancreata procured may not reflect a meaningful increase in pancreata being actually used for islet cell research, and instead may reflect pancreata procured for other purposes. This memo is clarifying that the pancreata must be used for islet cell research. 

...

"In summary, this memo is clarifying that consistent with the Pancreatic Islet Cell Transplantation Act of 2004, only pancreata procured by an OPO and used for islet cell transplantation or research shall be counted"

Tuesday, January 9, 2024

Brain death for organ donation, and its relation to controversy about abortion

 Here's a summary of the current discussion of brain death (and its possible connection to the debate on whether a fetus is a living person), in JAMA. Maybe it will reach some resolution this year...

Truog, Robert D., and David C.  Magnus. The Unsuccessful Effort to Revise the Uniform Determination of Death Act. JAMA. 2023;330(24):2335–2336. doi:10.1001/jama.2023.24475

"In 1968, a Harvard committee proposed a new approach for determining death, one based on the irreversible loss of neurological functions.1 This concept was instantiated into law in 1980 when the Uniform Law Commission endorsed The Uniform Determination of Death Act.2 The act, which a large majority of states have adopted in whole or with some variations, says, in part, that an individual is dead if the individual has sustained (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem. A determination of death must be made in accordance with accepted medical standards.

"In 2020, the commission was asked to consider updating the act, based in part on concerns that the act does not fully align with current medical practice.3 A draft of its revision was presented and discussed at the commission’s annual meeting on July 26, 2023.4 Herein, we summarize the major issues that led to the decision to draft a revision, the alternatives that were considered, why there was failure to reach consensus, and what this means for the future.

"The Uniform Determination of Death Act defines neurological death, commonly known as brain death, as the complete absence of all functions of the entire brain. The current diagnostic criteria, however, test for only a subset of brain functions, and most notably do not include testing for neurosecretory hypothalamic functions, which are retained by many patients who have been diagnosed as brain dead.5 In addition, the law requires the “irreversible” cessation of biological functions, whereas in practice the standard has been “permanence,” with the distinction being that irreversible implies that the function cannot be restored, whereas permanence means that the function will not be restored because no attempt will be made to do so.

...

"n order for medical practice to be in compliance with the law, the commissioners considered either changing the guidelines to conform with the law, or changing the law to conform with the guidelines. Under the first approach, the guidelines would require physicians to diagnose the irreversible cessation of all brain functions, not just selected functions. This would be challenging, given the difficulty of detecting and measuring all of the brain’s many functions. Alternatively, the law could be revised to be coherent with current practice guidelines. At the annual meeting of the Uniform Law Commission, the committee considered the following draft alternative to the existing Uniform Determination of Death Act4: “An individual is dead if the individual has sustained: (1) permanent cessation of circulatory and respiratory functions; or (2) permanent (A) coma, (B) cessation of spontaneous respiratory functions, and (C) loss of brainstem reflexes.”

"This proposal would harmonize the law with the practice guidelines. Instead of requiring the absence of all brain functions, this revision would have required only the absence of specific brain functions, namely the capacity for consciousness and spontaneous respiration.

"The proposed revision also would have replaced the requirement for irreversible cessation with permanent cessation, thereby anticipating the trajectory of new developments in resuscitation research, including work demonstrating the potential for restoration of neuronal function in brains, even many hours after the loss of brain perfusion.6 Using the permanence standard, death can be determined in these patients on the grounds that function will not be restored rather than the requirement that it cannot be restored.

"Finally, the proposed revision also included a section that would have required hospitals to respect the refusal of patients or their surrogates to having death determined by neurological criteria. This position was supported by various constituencies, including the Catholic Medical Association, as well as several of the Uniform Law Commission commissioners, who saw it as a way to respect the diversity of opinions surrounding the determination of death while still supporting the concept of brain death. At the same time, this approach was strongly condemned by most mainstream physician and transplant organizations, given the burden that it would place on hospitals and intensive care units and its potential negative impact on organ procurement.

...

"in an email on September 22, 2023, the committee leadership announced that they had decided to pause the process, saying that “although we will continue to hope mid-level principles will become apparent, no further drafting committee meetings will be scheduled at this time.”

"Perhaps this outcome could have been predicted from the beginning, given the polarization that has evolved in the US around issues at the beginning and end of life. Commissioner James Bopp emphasized these connections in asserting that the controversies around brain death and abortion are an “identical debate, just in a different context.”7

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Earlier:

Wednesday, October 18, 2023

Monday, January 8, 2024

"Scraping poison off the bone": Transplants in China without organs from executed prisoners

 Following a long period in which the bulk of China's organ transplants used organs from executed prisoners, there have been steady efforts to create a system of voluntary deceased donation comparable to that in most of the world where transplants are done.

Global Times has the latest bit of that evolving story:

China’s organ donation to be more transparent under newly issued rules By Zhao Yusha and Zhang Yuying   Dec 15, 2023

"Chinese Premier Li Qiang has signed a decree of the State Council to unveil rules on human organ donation and transplantation, media reported on Thursday, with Chinese experts noting that the country’s organ donations will be more transparent under the regulation, which reflects great determination in China's organ donation reform. 

The newly issued rules, which will take effect on May 1, 2024, have been refined from the ones on human organ transplantation issued in 2007 to meet the demands of changing situations and ensure the healthy development of the cause, according to the Xinhua News Agency.

The rules strengthen the publicity and guidance of organ donation. Besides, the regulations stipulate that organ donation must adhere to the principles of voluntary and unpaid participation, and the conditions and procedures of donation should be improved based on the Civil Code. 

...

"China’s organ donations will be more transparent under the newly issued rules, Huang Jiefu, chairman of China Human Organ Donation and Transplantation Committee and chair of the China Organ Transplant Development Foundation Advisory Board, told the Global Times on Thursday.

"Huang noted that the revision of the rules shows the great determination in China's organ donation reform, which he described as scraping poison off the bone. “The regulations reflect the importance the Party and country attach to organ donation, which provides a strong legal guarantee for the high-quality development of organ donation cause.” 

"According to the rules, the application management of organ transplantation technologies should be improved to ensure medical quality. Specifically speaking, the rules define the conditions that medical institutions and practicing physicians must possess when engaging in organ transplantation, and require regular evaluation of the clinical application capabilities of relevant technologies in medical institutions. 

...

"In addition, the rules improve related provisions on legal liabilities and strengthen the punishment of malpractice in the field, Xinhua reported.

"Experts said the new rules call for more people to get involved in organ donations and transplants, and it is hoped that China's organ transplantation technology will spread to more countries in the future."

********

Here (in Chinese, but with Google Translate) is the announcement from Xinhua News Agency

李强签署国务院令 公布《人体器官捐献和移植条例》"Li Qiang signed a State Council order announcing the "Regulations on Human Organ Donation and Transplantation"

[The new regulations] "stipulate that patients whose spouses, direct blood relatives and other relatives have donated deceased organs can apply for organ transplantation , priority is given to them under the same conditions. 

...

"Ethical review requirements before organ harvesting will be refined, and the witnessing procedures for harvesting organs from deceased persons will be stipulated. Improve the cadaver organ distribution system, stipulate that the distribution of cadaver organs should meet medical needs, follow the principles of fairness, impartiality, and openness, and distribute uniformly through the distribution system established by the health department of the State Council. It is required to regularly announce the donation and distribution of cadaver organs and accept social supervision.

...

"In addition, relevant provisions on legal liability have been improved, penalties have been increased, and illegal activities in the field of organ donation and transplantation have been severely cracked down on.

  "(Authorized release) Order No. 767 of the State Council of the People's Republic of China

  "(Authorized release) Regulations on Human Organ Donation and Transplantation"


HT: Michelle Miao

Friday, November 17, 2023

Report From a Multidisciplinary Symposium on the Future of Living Kidney Donor Transplantation

 How might we increase the number of lifesaving transplants from living kidney donors? Might we one day be able to reward donors? And what might we do until then, while we wait for something that will eventually replace human organ transplantation?  Here's the published account of last year's symposium.

Thomas G. Peters, John J. Fung, Janet Radcliffe-Richards, Sally Satel, Alvin E. Roth, Frank McCormick, Martha Gershun, Arthur J. Matas, John P. Roberts, Josh Morrison, Glenn M. Chertow, Laurie D. Lee, Philip J. Held, and Akinlolu Ojo, “Report From a Multidisciplinary Symposium on the Future of Living Kidney Donor Transplantation,” Progress in Transplantation  (forthcoming), Online first, Nov 15, 2023 https://journals.sagepub.com/doi/full/10.1177/15269248231212911  (pdf here).

Abstract: Virtually all clinicians agree that living donor renal transplantation is the optimal treatment for permanent loss of kidney function. Yet, living donor kidney transplantation has not grown in the United States for more than 2 decades. A virtual symposium gathered experts to examine this shortcoming and to stimulate and clarify issues salient to improving living donation. The ethical principles of rewarding kidney donors and the limits of altruism as the exclusive compelling stimulus for donation were emphasized. Concepts that donor incentives could save up to 40 000 lives annually and considerable taxpayer dollars were examined, and survey data confirmed voter support for donor compensation. Objections to rewarding donors were also presented. Living donor kidney exchanges and limited numbers of deceased donor kidneys were reviewed. Discussants found consensus that attempts to increase living donation should include removing artificial barriers in donor evaluation, expansion of living donor chains, affirming the safety of live kidney donation, and assurance that donors incur no expense. If the current legal and practice standards persist, living kidney donation will fail to achieve its true potential to save lives.

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Links to videos of the symposium presentations are here:

Sunday, November 5, 2023

Deceased organ donation in the Economist (article and letter to the editor)

 Here's a recent article on deceased organ donation, in The Economist, followed by a letter to the editor from Alex Chan and me.

In America, lots of usable organs go unrecovered or get binned. That is a missed opportunity to save thousands of lives

"More than four-fifths of all donated organs and two-thirds of kidneys come from dead people (who must die in hospital); living donors can give only a kidney or parts of a lung or liver. Whereas some countries, such as England, France and Spain, have an opt-out model, in America donors must register or their families must agree. Persuading them will always be hard: Dr Karp’s hospital gets consent from about half of potential donors.

...

"Responsibility lies partly with some of the 56 nonprofit Organ Procurement Organisations (opos), like LiveOnNY, that do the legwork. Brianna Doby, a researcher and consultant, advised Arkansas’s opo in 2021 and was astounded to learn that most calls about potential donors went unanswered outside the nine-to-five workday and at weekends. Other opos, by contrast, sent staff to hospitals within an hour of an alert about a prospective donor.

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"Yet unrecovered organs are not the only reason America could do more transplants. A surprising number of organs from deceased donors end up in the rubbish: more than a quarter of kidneys and a tenth of livers last year.

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"Hospitals are often risk-averse, too. Discard rates are higher for organs of lower quality.

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"For elderly recipients, getting older or otherwise risky kidneys generally means better odds of survival than staying on dialysis. But hospitals dislike using them for two reasons. First, they can lead to more complications and thus require more resources, eating into margins. Second, if the recipient dies soon after the transplant, hospitals suffer—a key measure used to evaluate them is the survival rate of recipients a year after transplant. According to Robert Cannon, a liver-transplant surgeon at the University of Alabama at Birmingham, hospitals succeed by being excessively cautious and keeping patients with worse prospects off waiting lists."

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And here's our followup letter to the editor, published November 2:

Organ-donation economics

"More than 110,000 Americans are waiting for an organ transplant and over 5,000 died waiting for an organ in 2019. Close to 6,000 recovered organs were discarded. “Wasted organs” (September 23rd) correctly pointed out that the responsibility lies in part with non-profit Organ Procurement Organisations and in part with the excessive caution exercised by transplant centres when deciding who to conduct transplants for and which kidneys to use.

"Numerous initiatives in Congress, and more proposed by various non-governmental agencies, such as the Federation of American Scientists and the National Academies of Sciences, Engineering and Medicine, among others, have been focused on tweaking how the performance of organ procurers and transplant centres should be measured while keeping in place the system that put us in today’s quagmire. As we indicate in our recent paper (conditionally accepted at the Journal of Political Economy), such approaches that keep regulations fragmented are bound to be inefficient, given that the incentives and opportunities facing organ procurers and transplant centres are intertwined.

"We show that “holistic regulation”, which aligns the interests of organ procurers and transplant centres by rewarding them based on the health outcomes of the entire patient pool, can get at the root of the problem. This approach also leads to more organ recoveries while increasing the use of organs for sicker patients who otherwise would be left without a transplant.

"In the end increasing access to kidney transplantation will require the improvement of the entire supply chain of organs. This means boosting donor registrations and donor recoveries from the deceased. It also means increasing living donations, and co-ordinating donations through mechanisms like paired kidney donations and deceased-donor-initiated kidney- exchange chains.


Alex Chan, Assistant professor of business administration, Harvard University

Alvin E. Roth, Professor of economics, Stanford University

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And here's the paper referred to in our letter, on Alex's website:

Regulation of Organ Transplantation and Procurement: A Market Design Lab Experiment, by Alex Chan and Alvin E. Roth

Abstract: "We conduct a lab experiment that shows current rules regulating transplant centers (TCs) and organ procurement organizations (OPOs) create perverse incentives that inefficiently reduce both organ recovery and beneficial transplantations. We model the decision environment with a 2-player multi-round game between an OPO and a TC. In the condition that simulates current rules, OPOs recover only highest-quality kidneys and forgo valuable recovery opportunities, and TCs decline some beneficial transplants and perform some unnecessary transplants. Alternative regulations that reward TCs and OPOs together for health outcomes in their entire patient pool lead to behaviors that increase organ recovery and appropriate transplants."

Monday, October 23, 2023

Waitlist equity, when not everyone can wait a long time, by Afshin Nikzad and Philipp Strack

 Patients waiting for deceased donor kidneys are given priority in part by how long they have been on dialysis, while patients waiting for livers are prioritized according to how sick they are, sickest first.  When the wait is long, not everyone has an equal chance of surviving long enough to receive an organ. Here's a paper that suggests that service in random order (SIRO) has desirable equity properties. Efficiency depends on how patients' welfare and future prospects change while they wait.

Equity and Efficiency in Dynamic Matching: Extreme Waitlist Policies, by Afshin Nikzad and Philipp Strack, Management Science, forthcoming, Published Online:3 Oct 2023https://doi.org/10.1287/mnsc.2023.01212

Abstract: Waitlists are commonly used to allocate scarce resources, such as public housing or organs. Waitlist policies attempt to prioritize agents who wait longer by assigning them priority points (à la first come, first served). We show that such point systems can lead to severe inequality across the agents’ assignment probabilities unless they use randomization. In particular, deterministic point systems lead to a more unequal allocation than any other rule that prioritizes earlier arrivals, an axiom that ensures that agents who wait longer are treated (weakly) better. Among the policies abiding by this axiom, we show that service in random order (SIRO) leads to the most equal allocation. From a utilitarian perspective, we show that the planner faces no trade-off between equity and efficiency when the flow utility from waiting is nonnegative or negative and increasing over time. In these cases, SIRO is also the most efficient policy. However, when the flow cost of waiting increases over time, then the planner may face an efficiency–equity trade-off: SIRO remains the most equitable policy but may not be the most efficient one.


1. Introduction: Waitlists are a common way to allocate scarce resources, such as public housing,1 organs,2 or services such as call center support.3 There are many ways to decide who among the waiting agents receives an object once it becomes available. Some waitlists operate in a service-in-random-order (SIRO) manner and use lotteries to allocate objects to waiting agents, such as in the Diversity Immigrant Visa Program in the United States4 or Beijing’s license plate allocation.5 Many other waitlists follow designs akin to first come, first served (FCFS), in which whoever has waited for the longest time receives (priority points for) an object. For example, in the national kidney transplant waitlist in the United States, enrolled patients earn priority points for each day that they remain on the waitlist.6 Such rules ensure that an agent who waits longer is not treated worse than an agent with a shorter waiting time and otherwise identical characteristics.

"Prioritizing agents with longer waiting times, however, has a drawback: it implies that an agent with a longer lifetime, that is, an agent who can wait longer for an object, has a higher probability of receiving an object. This naturally leads to inequality in assignment probabilities across agents with varying lifetimes. For example, a first-come, first-served list would lead to many of the sickest patients never receiving an organ as they depart the system before having waited long enough to receive an organ. Such equity concerns, for example, play an important role in the context of organ allocations (Organ Procurement and Transplantation Network 2015). The high-level question we ask here is, what policy induces the least inequality among policies that give priority to agents who arrive earlier? Furthermore, is minimizing inequality aligned with the objective of a planner who maximizes the average of the agents’ utilities, or are there efficiency–equity trade-offs to be considered here?"

Wednesday, October 18, 2023

Peter Singer on brain death

 Here's Peter Singer's op-ed in the Washington Post on the debate over brain death, presently used to decide when deceased donor organs can be used for transplantation:

What is the line between life and death? Here’s my answer.  By Peter Singer  October 17, 2023 

"When it is justifiable to end a human life?

"Here’s my answer: When consciousness has gone, never to return. Other bioethicists have different views. No surprise there. But on this we should all agree: These differences need to be hammered out in public, not behind closed doors by a body that few people have heard of.

"The last effort to define death in the United States was in 1980, and at that time there was remarkable consensus on a decision so consequential. Then, the commission proposed a new Uniform Determination of Death Act establishing that in addition to the traditional determination of death by the heart ceasing to beat, a person is dead when their whole brain has irreversibly ceased to function. All 50 states and D.C. adopted the act’s central proposition — which is staggering, really, given today’s battles over when life begins."

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Earlier:

Sunday, October 8, 2023

Sunday, October 8, 2023

Dead or alive? Debates about defining brain death and circulatory death in the medical literature

Before the invention of ventilator technology, circulatory death ('cardiorespiratory death') and brain death ('neurological death') were essentially the same thing, because one inevitably caused the other, very quickly.  But now that circulation can be maintained after the brain has gone irreversibly/permanently silent, we can make distinctions.  And some of those distinctions depend on the distinction between irreversibly and permanently.  This post starts with a position statement, but then features the underlying debate, and in fact two of the dueling papers take opposite stands on 'irreversible' and 'permanent.'. (The difference is that e.g. heart stoppage might be possibly reversible, but a 'do not resuscitate' order would mean that it was nevertheless permanent.) 

But before the debate, here's a position paper

Standards and Ethics Issues in the Determination of Death: A Position Paper From the American College of Physicians by  DeCamp, Matthew, Kenneth Prager, and American College of Physicians Ethics, Professionalism and Human Rights Committee, Annals of Internal Medicine (2023).

"Abstract: The determination of a patient’s death is of considerable medical and ethical significance. Death is a biological concept with social implications. Acting with honesty, transparency, respect, and integrity is critical to trust in the patient–physician relationship, and the profession, in life and in death. Over time, cases about the determination of death have raised questions that need to be addressed. This American College of Physicians position paper addresses current controversies and supports a clarification to the Uniform Determination of Death Act; maintaining the 2 current independent standards of determining death, cardiorespiratory and neurologic; retaining the whole brain death standard; aligning medical testing with the standards; keeping issues about the determination of death separate from organ transplantation; reaffirming the importance and role of the dead donor rule; and engaging in educational efforts for health professionals, patients, and the public on these issues. Physicians should advocate for policies and practices on the determination of death that are consistent with the profession’s fundamental and timeless commitment to individual patients and the public."

...

"Scientific advances motivate revisiting foundational concepts, including those around death and dying. Decades ago, advanced cardiorespiratory support—because of its ability to maintain cardiac and respiratory functions in individuals whose brain function was thought to have ceased—contributed to the development of brain death as a concept. Studies now show restoration of cellular and molecular activity in whole pig brains (without restoration of brain functions) 4 hours postmortem using an ex vivo perfusion system called “BrainEx” (15, 16). Today, a controversial protocol known as thoracoabdominal normothermic regional perfusion with controlled donation after circulatory determination of death can result in the resuscitation of the asystolic heart to restore circulation after what was a determination of circulatory death—to increase organ availability for transplant—but this invalidates the determination of death and breaches ethical boundaries (17, 18). Moreover, there has been ongoing advancement in ancillary tests, such as electroencephalograms, magnetic resonance angiography, single-photon emission computed tomography, hypothalamic testing (19), computed tomography angiography, computed tomography perfusion (20), and others. Results of these methods of testing can raise questions about the accuracy of clinical determinations of death.

...

"Position 1

ACP supports revising the Uniform Determination of Death Act (UDDA) to replace the word “irreversible” with “permanent” in the first clause to read, “An individual who has sustained either (1) permanent cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead. A determination of death must be made in accordance with accepted medical standards.”


"The UDDA (21) currently states, “An individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead. A determination of death must be made in accordance with accepted medical standards.”

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And here's a whole series of position papers in the journal Neurology: 

The Uniform Determination of Death Act (UDDA) Revision Series

This series aims to educate the neurology community about the most important brain death controversies the US Uniform Law Commission must consider in rewriting the UDDA.

Challenges to Brain Death in Revising the Uniform Determination of Death Act: The UDDA Revision Series
James L. Bernat

What Is the Ideal Brain Criterion of Death? Clinical and Practical Considerations: The UDDA Revision Series
Nathaniel M. Robbins

What Is the Ideal Brain Criterion of Death? Nonclinical Considerations: The UDDA Revision Series
Michael A. Rubin

Must Hypothalamic Neurosecretory Function Cease for Brain Death Determination? Yes: The UDDA Revision Series
Michael Nair-Collins

Must Hypothalamic Neurosecretory Function Cease for Brain Death Determination? No: The UDDA Revision Series
Panayiotis Nicolaou Varelas

Should the Criterion for Brain Death Require Irreversible or Permanent Cessation of Function? Irreversible: The UDDA Revision Series
Ari R. Joffe

Should the Criterion for Brain Death Require Irreversible or Permanent Cessation of Function? Permanent: The UDDA Revision Series
Andrew McGee, Dale Gardiner

Should the Brain Death Exam With Apnea Test Require Surrogate Informed Consent? Yes: The UDDA Revision Series
Ivor David Berkowitz, Jeremy Garrett

Should the Brain Death Exam With Apnea Test Require Surrogate Informed Consent? No: The UDDA Revision Series
David Greer

Potential Threats and Impediments to the Clinical Practice of Brain Death Determination: The UDDA Revision Series
Ariane Lewis, Matthew P Kirschen

Rethinking Brain Death—Why “Dead Enough” Is Not Good Enough: The UDDA Revision Series
Daniel P. Sulmasy, Christopher DeCock

Tuesday, October 3, 2023

Transplant grand rounds in Manitoba, tomorrow on kidney exchange

 I'll be talking tomorrow to the transplant pros in Manitoba, about kidney exchange and transplants across borders, among other things.

Wednesday, Oct 4, 2023 | 1:15 PM CST