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

Organ transplantation in China: in transition--and controversy about paying funeral costs

 I recently spoke at the CAST transplant conference in Hong Kong (see picture), and the underlying theme of my talk, and of many talks there, was the transition of transplantation in China, and what its future might hold.

Jie-Fu HUANG is the other speaker on Zoom (to my right and your left), and Haibo Wang is on the far left on stage.

Here are two of my opening slides (using 2021 data from the Global Observatory on Donation and Transplantation)

On the left, you see that, today, China and India already perform more kidney transplants than any country in the world except the U.S.  On the right, you see that, by virtue of their large populations, they accomplish this despite their quite low rates of transplants per million population, compared to the U.S. and countries in Europe.  So if China and India can raise their transplant rates to rates comparable to the U.S. and Europe, most of the transplants in the world will be done in Asia, and many many additional lives will be saved.

Note that China mostly transplants kidneys from deceased donors, while India mostly transplants kidneys from living donors. So they have different paths (and plenty of untapped potential) for raising donation and transplantation rates.  And their paths to their current positions have also been very different.

Here is a recent account reflecting China's recent progress:

Chen, Zhitao, Han, Ming, Dong, Yuqi, Zeng, Ping, Liao, Yuan, Wang, Tielong, et al. (2023). First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China: 5-year Experience at a High-volume Donor and Recipient Liver Transplant Center. Transplantation, 107, 1855-1859. https://doi.org/10.1097/TP.0000000000004561

" In 1972, our center performed the first living donor kidney transplantation in China. Since then, kidney and liver transplant programs have evolved. By the beginning of the 21st century, organ transplantation had advanced, and clinical liver transplants have been performed successfully at the First Affiliated Hospital of Sun Yat-sen University.1

"Organ shortage has been a prominent feature at our institution as it has been around the world. Starting in the early 1980s, many organs had been procured from inmates on death rows. This unethical approach has been rightfully criticized by the worldwide community. As a consequence, the source of organs for transplants has solely been replaced by voluntary donations from Chinese citizens since January 1, 2015.

...

"Moreover, policies and methods for humanitarian aid to donor families were established. Those policies follow WHO guidelines while recognizing specific aspects of the Chinese culture. The State Ministry of Health and the Red Cross Society of China launched a pilot project on organ donation after the death of citizens in 2010 and established the China Organ Donation Committee. The principle of this pilot project was to learn from the experiences and standards in developed countries while recognizing national conditions and the social reality in China aiming to build an ethical and effective scientific organ donation and transplantation system.2

**********

In the same issue of Transplantation as the above article is this invited commentary by Ascher and Delmonico, both former Presidents of The Transplanation Society (of which Transplantation is the official journal). They largely approve of the effort China has made in transplants, but they have a big reservation.

Ascher, Nancy, MD, PhD & Delmonico, Francis. (2023). Organ Donation and Transplantation in China. Transplantation, 107, 1880-1882. https://doi.org/10.1097/TP.0000000000004562

"The date of 2015 is important for the review of any organ transplantation report from China because of the public proclamation in the media in 2015 prohibiting the use of organs from executed prisoners. Clinical transplantation articles antecedent to 2015 have been consistently rejected by Transplantation and the international community because the source of the transplanted organs was most often an incarcerated prisoner. China took a major step to condemn this practice publicly in 2015. However, because there is no law or regulation that prohibits this unethical practice, there has been ongoing concern that this practice may be continuing. Notwithstanding such a reality, there have been regulations that are citable and may be reflective of the changing experience of organ donation and transplantation in China that are consistent with the World Health Organization (WHO) Guiding Principles.

...

"WHAT CONTINUES TO BE OBJECTIONABLE

"The Chinese Red Cross is prominent in the organ donation process and a center of support for deceased donor families designated by the Red Cross as humanitarian aid to donor families.7 However, such humanitarian aid, although not limited to China, should not be misinterpreted to be an effort because it includes payment to elicit consent for donation. The Sun Yat-sen publication suggests that the Red Cross policies follow WHO guidelines while recognizing specific aspects of Chinese culture without elaboration as to the cultural details. A payment to donor families for funeral expenses or other monetary incentives should be recognized as a form of commercialization and would not comply with WHO guidelines."

**********

Some background may help put this objection in perspective. Doctors Delmonico and Ascher are prominent signatories of a declaration that payments to families of organ donors are crimes against humanity (as are payments to living donors, and both are declared comparable to transplanting organs from executed prisoners, and to be organ trafficking. See my 2017 post.)

So, they raise the question of whether saving many lives by increasing deceased donation in China will be justified if it involves paying funeral expenses of donors.  

My guess is that Chinese health authorities, thinking of the many lives to be saved, will think that this act of generosity to families of deceased donors will indeed be justified, taking account of (see above) "national conditions and the social reality in China aiming to build an ethical and effective scientific organ donation and transplantation system." 

Many people in China and elsewhere might even think that little if any justification is needed for generosity, particularly generosity to families of deceased donors, that is to families who are themselves generous.

THE 18TH CONGRESS OF ASIAN SOCIETY OF TRANSPLANTATION (CAST) 25 -28 August 2023 • Hong Kong

Tonight, Sunday, at 5:30pm California time, I'll be opening the Monday morning session in Hong Kong of the THE 18TH CONGRESS OF ASIAN SOCIETY OF TRANSPLANTATION 25 -28 August 2023.

Keynote Lecture

28 Aug 0815-0915 Theatre 1 Keynote Lecture III

Chairs : Albert CY CHAN, Hong Kong, China

Hai-Bo WANG, Mainland China

Topic 1. Transplant economics Alvin ROTH USA

Topic 2. Organ transplantation reform in China: The synergy of Chinese cultural traditions and WHO guiding principle  Jie-Fu HUANG Mainland China

Kidney disease in war-torn Sudan

 The Lancet brings us this news from Sudan.

Kidney failure in Sudan: thousands of lives at risk by Hatim A Hassan, Mohamed Hany Hafez, Valerie A Luyckx, Serhan Tuğlular, and Ali K Abu-Alfa, The Lancet, August 09, 2023DOI:https://doi.org/10.1016/S0140-6736(23)01370-3

"Sudan is one of few countries in Africa that has provided dialysis and transplantation under universal health coverage for several decades.2 Before the war, around 8000 patients required ongoing dialysis and around 4500 were living with kidney transplants (appendix). Haemodialysis was provided twice per week instead of three times per week to permit access to more patients within budget constraints.3

Haemodialysis requires continuous water, electricity, staffing, and disposable supplies. Since fighting began, dialysis services, which are mostly located in Khartoum, have been severely disrupted (appendix). Patients who can, have fled to dialysis units in other cities. Despite some units reducing haemodialysis frequency to once weekly, shortening sessions at times to 2 h, and offering appointments all day and all night, they are struggling to cope with demand. Most haemodialysis staff continue to work without being paid and are at high risk of burn-out. Egypt is accepting patients needing dialysis, but the cost and risk of the journey are prohibitively high for most.

Dialysis supplies have mostly run out by early August, 2023, despite dialysis sessions being reduced to weekly. A donation of supplies for a third of the patients for 3 weeks was obtained from one company. Reliance on donations of the large quantities of dialysis supplies needed for around 8000 patients is unrealistic. Dialysis supplies are not only expensive, but are bulky and costly to transport. Patients with kidney transplants are experiencing dangerous interruptions in their access to immunosuppressive medication. A reliable source of financing is urgently required to meet the needs of patients requiring dialysis and people with kidney transplants.

Support is needed to prevent adding a further layer of tragedy to this war if dialysis services cannot continue and transplant medication is not provided. Wars elsewhere pose similar threats to dialysis provision. The global health agenda must address the urgent need for transparent decision making and affordable access to vital treatments such as dialysis and transplantation during crises. Finding solutions to meet the needs of patients with kidney failure who depend on these therapies in low-resource settings in times of peace is also long overdue."

Organ transplants between Hong Kong and mainland China: the promise and the politics

 This is a followup post to an earlier post# about the first cross border transplant in China between the mainland and Hong Kong. That's been followed by some political tensions, as reported in this forthcoming article in the American Journal of Transplantation.

A plan to save lives: Hong Kong–mainland China second-tier mutual assistance allocation. The new program between the transplant communities plays out on a backdrop of controversy and historical tension  by Lara C. Pullen, PhD, Published:July 28, 2023DOI:https://doi.org/10.1016/j.ajt.2023.07.015

"Key points:

"The transplant communities of Hong Kong and mainland China have proposed a second-tier mutual assistance allocation program that some find controversial.

• Tensions between Hong Kong and mainland China have a long and deep history.

• In 2014, the Chinese government announced a stop to obtaining organs from executed prisoners.

• Transplantation in mainland China has rapidly evolved, and people monitoring the change report that data from 10 to 15 years ago does not reflect the country’s current system."

**********

The background:

In December, the South China Morning Post carried this story about a transplant involving an organ recovered on the mainland and transplanted into a baby in Hong Kong, which was apparently the first such  transplant to cross that border:

4-month-old Hong Kong girl suffering from heart failure receives successful transplant with donated organ from mainland China, in city’s first such arrangement by Cannix Yau

One of the subheadlines is "Health Bureau notes importation of organ met relevant regulations, and hospital officials say arrangement involving mainland might be repeated in future"

***

And here's the story in the China Daily:

Securing a new lease of life By Li Bingcun | HK EDITION | Updated: 2023-03-31 15:10

"Hong Kong and the Chinese mainland have successfully carried out the first-ever cross-boundary organ-sharing operation, saving the life of an infant. The feat caps the city’s strenuous efforts to create a standing mechanism in organ sharing with the mainland to save more lives. Li Bingcun reports from Hong Kong."

***

Apparently the discussion of closer cooperation between transplant authorities in Hong Kong and the mainland is politically fraught. 

Here's a story from the Global Times that refers to some pushback from the mainland:

First organ donation between mainland and HK saves 4-month old baby By Wan Hengyi

"the acceptable heart donation for Cleo requires a donor weighing between 4.5 kilograms and 13 kilograms, and the chances of a suitable donor appearing in Hong Kong are slim to none. 

...

"COTRS initiated the allocation of a donated heart of a child with brain death due to brain trauma in the mainland on December 15. As a very low-weight donor, no suitable recipients were found after multiple rounds of automatic matching with 1,153 patients on a national waiting list for heart transplants in the COTRS system. In the end, the medical assistance human organ-sharing plan between the Chinese mainland and Hong Kong was launched.

"Some netizens from the Chinese mainland asked why a baby from Hong Kong who has not lined up in the COTRS system can get a donated heart when there is a huge shortage of donated organs in the mainland.

"In response, the organ coordinator told the Global Times that the requirements for organ donation are extremely high, noting that all the prerequisites including the conditions of the donor and recipient, the time for the organ to be transported on the road and the preparation for surgery must reach the standards before the donation can be completed.

"The COTRS system has already gone through several rounds of matching, which is done automatically by computer without human intervention, said the organ coordinator. "

...

"As of the end of October 2022, a total of 42,500 donors had donated more than 126,300 large organs in China, according to Guo Yanhong, director of the medical emergency department of the NHC."

******

Here's a story from the Guardian, about political concerns on the Hong Kong side:

Hongkongers opt out of organ registry ‘amid fear of Chinese donations’      by Amy Hawkins

"Thousands of Hongkongers have opted out of the city’s organ donor registry, seemingly as a form of subtle protest against proposals to establish deeper medical ties with mainland China.

...

"The trigger appears to have been a life-saving operation carried out in December on a four-month-old baby girl in Hong Kong, who was in need of a heart transplant. When a local match could not be found, a heart was transferred from a child who had suffered brainstem death in mainland China.

...

"Since the baby’s heart transplant, authorities have discussed the idea of establishing a mutual assistance registry with mainland China to facilitate future donations. That would be yet another erosion of the boundary between China and Hong Kong, which was supposed to remain largely autonomous from Beijing until 2047.

"Earlier this month, local news outlet Ming Pao reported that there had been discussion on social media among Hongkongers who did not want their organs donated to patients in mainland China."

********

China has a population approaching 1.5 Billion people, and Hong Kong is a city of about 7.5 Million people, so my guess is that HK is too small to have an efficient self-contained transplant system, and could benefit from being integrated into the mainland's system.

********

#Here's my earlier (contemporaneous) post:

Tuesday, January 10, 2023

Cross-border transplantation between China and Hong Kong

Freezing (and then carefully warming) donor organs breaks the organ transplant time barrier (for rats, for the time being)

 Here's a note in Nature Reviews Nephrology pointing out the longer term promise of the recent successful freezing, thawing, and transplantation of rat kidneys.

Cryopreservation breaks the organ transplant time barrier by Marlon J. A. de Haan & Ton J. Rabelink, in Nature Reviews Nephrology (2023)

"The pressing issue of organ shortages for transplantation is fuelled by the rising incidence of kidney failure and the declining quality of organs from an ageing donor pool. However, the main bottleneck in organ transplantation is time; indeed, the current clinical standard for kidney preservation necessitates immediate transplantation following organ recovery1. This urgency often results in suboptimal matches between donors and recipients. Cryopreservation has emerged as a potential solution to this challenge. Such an approach would enable organs to be preserved in a suspended state for extended periods and ready for transplantation on demand. The prospect of long-term banking of cryopreserved organs holds promise for transforming organ transplantation into an elective procedure, thereby enhancing donor–recipient matching, improving equity in access, optimizing patient preparation, refining transplant tolerance protocols, increasing organ utilization and improving graft and patient survival. However, even though cryopreservation has successfully been used to store human embryos, extending the process to preserve whole organs has remained a scientific aspiration — until now. A study by Han et al. introduces an approach to cryopreservation that seemingly extends the shelf life of organs indefinitely2."

...

"By rapidly cooling rat kidneys to –150°C, Han et al. were able to halt the biological clock of the organs, effectively inducing a glass-like state — a process known as vitrification2 (Fig. 1). Specifically, the researchers perfused a cocktail of cryoprotective agents (CPAs) and iron oxide nanoparticles into the organ’s vasculature, which they followed by rapid cooling to ultralow temperatures to achieve a state of vitrification. This vitrified kidney, with its hard, smooth, glasslike appearance, was then transferred to a –150°C freezer for long-term banking. When these kidneys were later rewarmed and transplanted into nephrectomized recipients, they regained life-sustaining renal function. The rewarming stage poses more challenges to the process of cryopreservation: it requires both speed to avoid ice formation during devitrification and uniformity to prevent thermal stresses and mechanical cracks. Here, the iron oxide nanoparticles had a crucial role. Placing the vitrified kidney in a coil that generates electromagnetic fields activates these nanoparticles, generating heat. This innovative approach enabled rapid rewarming at an impressive rate of approximately 72 °C per minute throughout the entire organ, ensuring uniform warming rather than limiting warming to the organs’ surface. This ground-breaking milestone marks an extraordinary achievement in ‘reviving’ a complex organ like the kidney and is the culmination of decades of research into methods to prevent the destructive formation of ice during the cooling process, minimize toxicity from CPAs, and enable fast and uniform rewarming3.

***********

Recently:

Wednesday, June 28, 2023

Freezing, thawing and transplanting a rat kidney: a first step towards organ banking

Ned Brooks on Coalition to Modify NOTA

Ned Brooks (about whom I've often blogged) is putting his eloquence and organizational skills to the task of increasing organ donation by allowing organ donors to be compensated. Below is a short video of an address he gave to the National Kidney Donation Organization (NKDO) which he founded, about his new effort, the Coalition to Modify NOTA.

 

Here's a copy of the email that came with the video:

To the NKDO Membership:   Thank you for your responses to the survey asking if NKDO should support the Coalition to Modify NOTA (CMN), formed by non-directed donors Ned Brooks, Elaine Perlman and Cody Maynard.   87% of our membership supports the mission statement of CMN as follows:   The Coalition to Modify NOTA (ModifyNOTA.org) is created in response to the inability of the current system to adequately address the crisis of kidney failure in the United States. The National Organ Transplant Act of 1984 prohibits the compensation of organ donors.   The current system of deceased donations and voluntary living donation is grossly inadequate to the task of completely ending the shortage of transplant kidneys and saving the lives of patients in kidney failure who are dying unnecessarily each year.  We believe that the solution to this crisis is to have the government compensate donors in a manner that is neither exploitative nor coercive. The Coalition to Modify NOTA seeks the modification of the National Organ Transplant Act to allow such government compensation.   Watch this presentation on the Coalition to Modify NOTA by Ned Brooks.   To sign your name in support of the Mission Statement, please go to Join the Coalition.   Kind regards,   Matt Cavanaugh, CEO and President

Senate Finance Subcommittee on Health Care --testimony on organ transplants, going on now

Watch right now or listen later.  UNOS is not popular in the Senate.

 https://www.c-span.org/video/?529461-1/health-advocates-testify-improving-organ-transplant-system

JULY 20, 2023

Health Advocates Testify on Improving Organ Transplant System

Patients and health professionals testify on the effectiveness of the organ transplant system before the Senate Finance Subcommittee on Health Care.

Report Video Issue

Watch live Watch from beginning

0 seconds of 58 minutes, 8 secondsVolume 50%

 

2:26:46

Share Video

Copy the Video URL below.

• Share This Video

• Clip
• Bookmark To MyC-SPAN
•  Clipping Guide

HOSTING ORGANIZATION

• Senate Finance Subcommittee on Health Care

More information about

Health Advocates Testify on Improving Organ Transplant System

Purchase a Download

Health Advocates Testify on Improving Organ Transplant System

x

x

Another set of links:Subcommittee Hearing

The Cost of Inaction and the Urgent Need to Reform the U.S. Transplant System

Subcommittee on Health CareDate: Thursday, July 20, 2023Time: 10:00 AMLocation: 215 Dirksen Senate Office Building

Cryopreservation of organs for transplants, and Sebastian Giwa in Forbes

 Forbes has a long, interesting, somewhat breathless story about the progress and promise of freezing organs for transplants, including not only the usual eight organs, but also bone marrow/blood stem cells. It focuses on one of the entrepreneurs in the field, Dr. Sebastian (Seb) Giwa, and his colleague Jedd Lewis among others

New Breakthroughs In Cryopreservation Poised To Transform Organ Transplantation, by Alex Zhavoronkov, PhD, Jul 5, 2023

"To understand how this came about I delved into the career of the founder and CEO of Sylvatica Biotech, Dr. Sebastian Giwa (called “Seb” by his friends). Seb is credited by many as the chief architect of the surge of scientific interest in cryopreservation over the last several years.

Sebastian Giwa, PhD, MBA 

BRIDGET BENNETT

...

"Trying to donate organs (without cryopreservation) is a lot like trying to donate perishable (non-canned) food: there are certainly a lot of starving people in the world, but good luck finding a recipient for every single ounce before it expires. 

...

"[Organ Preservation Alliance]  partnered ... to publish position papers, including a peer-reviewed article in Nature Biotechnology outlining the need for an organ cryopreservation research effort. The paper was co-authored with all of the major U.S. transplant societies and a star-studded lineup of scientists including Robert Langer, George Church, and Ed Boyden, and even Nobel Prize-winning economist Alvin Roth – whose work has focused on finding new ways to ameliorate the organ shortage. It is currently in the top 1% of the most widely read scientific articles published since its release.

...

"Donor bone marrow is lifesaving for many kinds of  cancers and a variety of other blood diseases. Successful bone marrow transplants have been performed since the 1950s, but the challenge is finding a source of bone marrow to transplant – especially since donors and recipients must be matched for genetic factors even more precisely than some organ transplants.

...

" if bone marrow could be cryogenically banked, why not procure it from deceased organ donors who were already providing hearts, livers, and other organs for transplantation? There are nearly 40,000 such donors worldwide each year, and each could potentially donate enough marrow for multiple patients in need. For many patients, when a transplant was needed the matching bone marrow would already be available in the bone marrow bank.

"From the perspective of the deceased organ donor and the OPOs, this would be like providing an opportunity to donate an additional lifesaving organ. Traditionally, each donor can provide up to eight lifesaving vital organs: a heart, two lungs, two kidneys, a liver, intestines, and a pancreas. In essence, bone marrow would be the ninth. And if a donor could provide bone marrow to multiple recipients, this might even double the number of lives that each donor could save.

...

"Alex: What’s something we haven’t covered that excites you about what cryopreservation can do for the organ shortage?

"Seb: In the long-term, one of the things that I’m most excited about is how these technologies can remove barriers to developing transplant systems in new countries. Most of the world still doesn’t have access to deceased donor transplantation. For instance, Africa has 16% of the world’s population but only 0.5% of transplants are done there. Meanwhile the U.S. has less than 5% of the world’s population but does about 25% of the world’s transplants. Many developed countries, like my father’s home country Ghana, have limited live kidney donation programs. But they don’t have deceased donor programs, which are needed to carry out large numbers of kidney and liver transplants as well as any sort of heart or lung transplantation.

"That’s partly because the logistical demands to source organ donations prospectively require so much infrastructure: a waitlist, rapid matching of donors to recipients, OPOs that need to be overstaffed in order to deal with unpredictable surges in organs available, rushed activities that require tight coordination between donor hospitals, OPOs, transplant centers, and even third party service providers like organ couriers. Many organs have also needed expensive transportation (private jets and helicopters).

"It’s a very different situation when there’s a source of cryopreserved hearts, livers, etc., that can be donated in a much more flexible way and are simply waiting to be matched to patients. Even things like Doctors without Borders and perhaps “OPOs without Borders” become possible for transplantation, helping train and develop new organ recovery, heart, lung, and liver transplant programs. So many more possibilities open up when you don’t need to create every part of a transplant system from scratch and have all of those parts acting in synchrony on Day 1."

**************

Here's the original article referred to:

The promise of organ and tissue preservation to transform medicine 
 Sebastian Giwa, Jedediah K Lewis, Luis Alvarez, Robert Langer, Alvin E Roth, George M Church, James F Markmann, David H Sachs, Anil Chandraker, Jason A Wertheim, Martine Rothblatt, Edward S Boyden, Elling Eidbo, W P Andrew Lee, Bohdan Pomahac, Gerald Brandacher, David M Weinstock, Gloria Elliott, David Nelson, Jason P Acker, Korkut Uygun, Boris Schmalz, Brad P Weegman, Alessandro Tocchio, Greg M Fahy, Kenneth B Storey, Boris Rubinsky, John Bischof, Janet A W Elliott, Teresa K Woodruff, G John Morris, Utkan Demirci, Kelvin G M Brockbank, Erik J Woods, Robert N Ben, John G Baust, Dayong Gao, Barry Fuller, Yoed Rabin, David C Kravitz, Michael J Taylor & Mehmet Toner

Nature Biotechnology 35, 530–542 (2017) doi:10.1038/nbt.3889
Published online 07 June 2017

Abstract: The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science.

************

Here's a recent related post:

Wednesday, June 28, 2023

Freezing, thawing and transplanting a rat kidney: a first step towards organ banking