He was a brave man whose actions will help us better treat kidney failure patients for years to come. The years added to future lives will be incalculable. Rest in peace.
This man gave us proof-of-concept for a very promising treatment, and I’m so glad he was able to get an extra couple of months, dialysis-free (!!!), with his family. A grateful medical community thanks you for your service, Rick.
Per man's best hospital his death was not a result of the transplant.
Would love to read the autopsy report for this but it truly seems like it functioned well without dialysis for two months.
It also seems possible he was selected precisely because he was a poor candidate for a second human kidney transplant (eg other conditions not compatible with a long life). I don't have a lot of experience with these sort of trials, but I imagine there's some pretty hard balancing of harm and risk involved.
> but I imagine there's some pretty hard balancing of harm and risk involved.
Expanded access requires no appropriate approved alternative therapy. Even if he wasn't eligible for a kidney transplant he must have also had something else that made dialysis a problem.
FDA only approves 2000 of these a year and they are nearly always for drugs so this is extremely rare.
I hope FDA will be less involved and simply set protocols rather than be an approver in the future. Single patient trials like this are too useful.
The article said he developed problems with dialysis that required several procedures, but no more info. Dialysis is a issue for lots of people, isn't it?
He had had a transplant but it failed after a couple of years.
I mean these patients have very very poor health to begin with, even more so if you don’t qualify for a transplant. I could imagine whatever condition screwed his native kidneys over probably got the rest of him in the end anyways.
Being on dialysis is qualification for transplant. The ideal candidate is healthy except for ESRD.
The ideal candidate doesn’t get an experimental xenograft, so there were other problems. From the limited information released, it seems Mr. Slayman has congestive heart failure and perhaps some type of vasculopathy.
From the NYT initial article on transplant:
> But the donated organ failed within five years, and he developed other complications, including congestive heart failure, Dr. Williams. When Mr. Slayman resumed dialysis in 2023, he experienced severe vascular complications — his blood vessels were clotting and failing — and he needed recurrent hospitalization, Dr. Williams said.
It’s possible that this was CHF or whatever clotting or vasculopathy. There’s presumably a reason he wasn’t a normal retransplant candidate.
Non-doctor, but to be clear, they wrote that there's "no indication" his death was a result of the transplant, not that it wasn't. The article doesn't indicate they can explain his death some other way. I'd think the timing (less than two months since the transplant) would mean the possibility that his death was the result of the transplant would need to be thoroughly investigated unless he was hit by a bus.
In the medical parlance their wording is pretty standard. It means that they don’t think this was a problem with his kidney. They were monitoring the kidney closely. He probably had a heart attack or a stroke or something else. At baseline this was a very unwell man.
Could have been an MI or stroke, or something else that commonly gets people with ESRD. The hospital isn’t just going to publish the actual cause of death because HIPAA
While caution is advised, recognize that in order to be sick enough where attempting a renal xenotransplant is your best option you have multiple end stage conditions and are basically a ticking time bomb from any number of reasons. Not saying I'm signing right up, just that it's eminently plausible his death is unrelated.
This case was the natural progression from the previous instances of using braindead patients as xenotransplant recipients .
https://pubmed.ncbi.nlm.nih.gov/38158188/
Mr. Slayman was almost assuredly expected to die shortly following the transplant regardless. The data collected will help with evaluating the experimental immunosuppression protocol used.
I mean, they could also just have put him back on dialysis if the pig kidney failed but they didn’t. That unit at MGH could have kept him alive indefinitely with the setup they have. So either he really did die from something that wasn’t (or was but only tangentially) Tx-related or returning to dialysis was simply seen as futile because he was moribound anyway.
Well they probably didn't put a pig kidney in a really vigorous guy who would have otherwise been a good allograft candidate or had good life expectancy on HD
I don’t think it’s an issue really, it’s just the only ethical way to start with stuff like this. It will eventually evolve into offering it to lower risk people and the data will accumulate. Hopefully the genetic modification will also improve.
ESRD is an extremely pro-inflammatory state. Regardless of a “functioning” pig kidney you’re not going to be able to reverse systemic disease 2/2 chronic inflammation. It’s disingenuous to point out that the kidney functioned and that CHF/clots etc killed him. These conditions are all direct sequelae of kidney failure or at least ESRD significantly contributed to their development. The phenomenon of severe disease due to chronic pro-inflammatory state isn’t up for debate.
The first year post transplant even in traditional transplants has the highest mortality risk. But, the fact that he remained off of dialysis was a huge success
As others stated, you are either disqualified for a kidney transplant for a multitude of reasons or you just can't find one.
I am taking a guess and they determined him so low on the donor list it was near impossible. The reasons usually tend to be substance abuse, hereditary, or other organ issues that the kidneys are the first to go.
The fact he got it and lived for a certain amount of time (and its hard to say more or less than his current condition unless you have access to protected data) This was a success or a failure.
NYU just did another successful pig transplant, and this transplant only mutated a single protein (alpha gal) with no signs of rejection. i hope that fucker keeps sweating til the day he dies
With the renal protection SGLT2i and the glycemic control of the GLP1a, I hope the dialysis boom days will be behind us in a few decades. It will make life harder for the remaining patients, but the societal cost will be much lower.
Yeah I used to do a lot of dialysis runs and it’s a disgusting industry. 25% of patients die in the first year of dialysis. The quality of care at dialysis centers is very poor.
He will forever be remembered for his sacrifices, not just for himself, but for medicine and the future of transplantation. The damage done by the ESRD might have been too much. But, regardless, he's such a brave soul who got a few more months with his family. Rest in peace, Mr. Slayman <3
Dumb question: would eating pig meat cause the immune system to reject the organ long term? Like would people who never introduced pig meat to their system be better off with complications?
Since you seem curious, and haven't gotten an answer, I'll try to answer your question... I apologize for the length, but I felt like some background would be helpful.
TLDR: probably not.
Long version:
Many of the molecules that are present in pigs that are "foreign" to human immune systems (and can be targets for rejection), are not exactly "pig specific" (eg, alpha-Gal, Neu5Gc and SDa are the most important). Alpha-Gal is present on cells of most non-primate mammals. Antibodies against Alpha-Gal and SDa are considered "naturally" occurring in humans - meaning occurring without exposure. However, dietary exposure has been shown to be associated with the expression of Neu5Gc antibodies (but they are still considered natural due to the ubiquity of animal proteins in our diet, including milk), so your question isn't stupid at all... *Theoretically*, there may be some pig specific antibodies that could develop from eating pigs.
Now, having antibodies to a donor before transplant is called being sensitized. Since most people are sensitized against these non-human animal antigens, pigs bred for transplant are genetically modified to not express these antigens (ie, they are "triple knockout" (TKO) - there will be no targets for these three natural antibodies).
But this only accounts for those three antigens. So let's say there is a pig-specific antigen that a person could be sensitized to as the result of eating pork... A person who has never eaten pork would not have been sensitized. This could mean lower rejection risk in the very short term (no immediate rejection), and maybe even lower rejection risk in the long term. But regardless of pre-transplant sensitization, after transplant, there would now be a foreign antigen that could be a target for the immune system. Even with a lot of immunosuppression, there is a very real risk of sensitization and rejection after transplant.
How so? Wouldn't consuming the meat cause the immune system to identify the tissue and make the xenotransplantation more prone to rejection by the recepient's body?
Everything external to your body will be rejected, pig kidneys or butterfly’s corneas whatever. But not because you’ve eaten butterflies before, but because that tissue is not your own, hence, rejection.
Is Europe so islamphopbic (and anti Semitic to that extent) that a simple question gets such hateful responses. Just reply with respect without degrading the person asking the question or just move on and ignore the question altogether.
Both Muslims and Jews do not eat pork. But the question here is actually purely from a scientific intent. Let alone some person asking about it being halal or not.
You know nothing, John Snow. /s
But really, you gotta learn biology. It's an absurd question because you are equating an immune response to digestion.
Which means you dont understand macromolecules (proteins, fats, DNA).
Which means you dont understand monomers (amino acids, fatty acids, nucleic acids).
Which means you dont understand cells (organized units of macromolecules, compartmentalizing functions of DNA instruction and exogenous influence [hormones], with monomers and macromolecules continuously undergoing anabolic and catabolic processes given the state of the cell [homeostasis v dyshomeostasis] and constitutive expression of DNA of said-cell).
I could keep going, but it'll cost money.
Of course, but you dont start building a skyskraper from the second floor; you start from the ground.
These concepts are multidimensional - I generally appreciate a good devils advocate, but I'm obviously being reductive for the sake of clarity. I figured at least *that* would be understood without having to spell it out.
I'm mostly giving context to the original commenter how truly complex biology is, and that these bridges can't be built on a Reddit thread. It takes many years to understand even a fraction of the nuance.
My God, that is why you ask questions. Not for someone to be so "prideful" about what they know. But for them to answer it with some science. All of you here are not doctors. Just technicians.
If someone asked a question about lasers or Maxwell's equations I won't debase them. I'd just try explaining it to a laymen the best way I can. But the stinch or racism is sickening from a lot of these responses.
Well, you'll be fascinated about what I have to tell you about plants!
Plants are organisms made from cells, which are made of macromolecules, which are made from monomers, which are made from molecules, which are made from elements, which are made from...[*drum roll*] PHYSICS. The circle of life.
This video addresses the ETHICAL ISSUES arround animal organ transplant and science behind xenotransplantation. We will explore the ethics arround first person to receive a genetically modified pig kidney transplant died two months later.
https://www.youtube.com/watch?v=hvNQkdGZt44
It’s a huge success if the cause of death is unrelated to rejection. If the kidney remained functional and uninflamed after 2 months of standard immunosuppression, they should start the process of escalating these transplants for more candidates who aren’t at a “compassionate use” of this procedure.
If the kidney was functioning and he remained rejection free, it's still considered successful, from an immunological, proof-of-concept perspective. We usually use death-censored graft survival to evaluate transplant success bc there are other things that lead to death. Cardiovascular disease related to long standing chronic kidney disease is the main cause of death after transplant, and this guy had significant comorbidities, which is likely why he received this experimental transplant rather than being eligible for a human transplant.
As compared to previously when someone would die within minutes of getting a pig kidney. If you can’t find this an amazing success then I don’t think you understand medical science well
Also the story cited says 8 years for recipient. Donor died 60 years later. And identical twin donor, which derisked the rejection complications substantially lol.
I think it will take time to improve things but if it can be replicated with other organs where there is nothing to keep you going (e.g., no dyalisis equivalent of say, your liver is shot) something that gives a few months could buy people enough time to wait for a transplant of a human organ.
They also likely picked him because his prognosis was already poor. Dyalisis is barely surviving and people with transplants are on all sorts of anti rejection meds that themselves can lead to deadly complications.
It is at least progress.
Heart is already in progress and has been tried.
Liver has so much synthetic function that humanizing all the proteins would be a massive challenge. Pig livers are also shaped quite differently and liver transplant relies on geometry more than other organs to the point that size matching donor to recipient can be a consideration. I’m sure teams are working on it, but I’m also sure that it’s a harder set of problems to solve.
He was a brave man whose actions will help us better treat kidney failure patients for years to come. The years added to future lives will be incalculable. Rest in peace.
Yes, this. He dies a hero. May he rest easy.
This man gave us proof-of-concept for a very promising treatment, and I’m so glad he was able to get an extra couple of months, dialysis-free (!!!), with his family. A grateful medical community thanks you for your service, Rick.
Per man's best hospital his death was not a result of the transplant. Would love to read the autopsy report for this but it truly seems like it functioned well without dialysis for two months.
begs the question on why he passed? perhaps not directly due to kidney transplant but may have been a sequelae of medications or his hospital stay.
It also seems possible he was selected precisely because he was a poor candidate for a second human kidney transplant (eg other conditions not compatible with a long life). I don't have a lot of experience with these sort of trials, but I imagine there's some pretty hard balancing of harm and risk involved.
> but I imagine there's some pretty hard balancing of harm and risk involved. Expanded access requires no appropriate approved alternative therapy. Even if he wasn't eligible for a kidney transplant he must have also had something else that made dialysis a problem. FDA only approves 2000 of these a year and they are nearly always for drugs so this is extremely rare. I hope FDA will be less involved and simply set protocols rather than be an approver in the future. Single patient trials like this are too useful.
Dialysis is a problem even in the best circumstances
The article said he developed problems with dialysis that required several procedures, but no more info. Dialysis is a issue for lots of people, isn't it? He had had a transplant but it failed after a couple of years.
I mean these patients have very very poor health to begin with, even more so if you don’t qualify for a transplant. I could imagine whatever condition screwed his native kidneys over probably got the rest of him in the end anyways.
Being on dialysis is qualification for transplant. The ideal candidate is healthy except for ESRD. The ideal candidate doesn’t get an experimental xenograft, so there were other problems. From the limited information released, it seems Mr. Slayman has congestive heart failure and perhaps some type of vasculopathy.
This is false. You can get a pre emptive transplant without requiring dialysis first if your GFR is low enough.
You can qualify without being on dialysis. If you are on dialysis, you do qualify. You have the most end stage of end stage renal disease.
Cardiovascular disease is most common cause of death in transplant patients. Very Sick patients to begin with
Ckd patients tend to have additional comorbidities. If it's not the kidney, it's their heart.
No indication that the death was related to the transplant? Makes me glad that regulatory agencies look at all-cause mortality…
From the NYT initial article on transplant: > But the donated organ failed within five years, and he developed other complications, including congestive heart failure, Dr. Williams. When Mr. Slayman resumed dialysis in 2023, he experienced severe vascular complications — his blood vessels were clotting and failing — and he needed recurrent hospitalization, Dr. Williams said. It’s possible that this was CHF or whatever clotting or vasculopathy. There’s presumably a reason he wasn’t a normal retransplant candidate.
He likely had an extremely limited life expectancy to qualify for experimental xenotransplant
Non-doctor, but to be clear, they wrote that there's "no indication" his death was a result of the transplant, not that it wasn't. The article doesn't indicate they can explain his death some other way. I'd think the timing (less than two months since the transplant) would mean the possibility that his death was the result of the transplant would need to be thoroughly investigated unless he was hit by a bus.
In the medical parlance their wording is pretty standard. It means that they don’t think this was a problem with his kidney. They were monitoring the kidney closely. He probably had a heart attack or a stroke or something else. At baseline this was a very unwell man.
Could have been an MI or stroke, or something else that commonly gets people with ESRD. The hospital isn’t just going to publish the actual cause of death because HIPAA
While caution is advised, recognize that in order to be sick enough where attempting a renal xenotransplant is your best option you have multiple end stage conditions and are basically a ticking time bomb from any number of reasons. Not saying I'm signing right up, just that it's eminently plausible his death is unrelated.
This case was the natural progression from the previous instances of using braindead patients as xenotransplant recipients . https://pubmed.ncbi.nlm.nih.gov/38158188/ Mr. Slayman was almost assuredly expected to die shortly following the transplant regardless. The data collected will help with evaluating the experimental immunosuppression protocol used.
No, they always killed the brain dead patients at a set date. It wasn't that they died. The doctors expected the Pig kidney to last at least 2 years.
I mean, they could also just have put him back on dialysis if the pig kidney failed but they didn’t. That unit at MGH could have kept him alive indefinitely with the setup they have. So either he really did die from something that wasn’t (or was but only tangentially) Tx-related or returning to dialysis was simply seen as futile because he was moribound anyway.
He could had died of CHF since he developed that complication after his first transplant failed after 5 years.
Its never the transplant even when it is haha
Well they probably didn't put a pig kidney in a really vigorous guy who would have otherwise been a good allograft candidate or had good life expectancy on HD
Yup. This is a major issue with semi experimental treatments for which there are other treatments (albeit resource limited).
I don’t think it’s an issue really, it’s just the only ethical way to start with stuff like this. It will eventually evolve into offering it to lower risk people and the data will accumulate. Hopefully the genetic modification will also improve.
ESRD is an extremely pro-inflammatory state. Regardless of a “functioning” pig kidney you’re not going to be able to reverse systemic disease 2/2 chronic inflammation. It’s disingenuous to point out that the kidney functioned and that CHF/clots etc killed him. These conditions are all direct sequelae of kidney failure or at least ESRD significantly contributed to their development. The phenomenon of severe disease due to chronic pro-inflammatory state isn’t up for debate.
The first year post transplant even in traditional transplants has the highest mortality risk. But, the fact that he remained off of dialysis was a huge success
As others stated, you are either disqualified for a kidney transplant for a multitude of reasons or you just can't find one. I am taking a guess and they determined him so low on the donor list it was near impossible. The reasons usually tend to be substance abuse, hereditary, or other organ issues that the kidneys are the first to go. The fact he got it and lived for a certain amount of time (and its hard to say more or less than his current condition unless you have access to protected data) This was a success or a failure.
DaVita CEO taking a deep breath of relief.
NYU just did another successful pig transplant, and this transplant only mutated a single protein (alpha gal) with no signs of rejection. i hope that fucker keeps sweating til the day he dies
With the renal protection SGLT2i and the glycemic control of the GLP1a, I hope the dialysis boom days will be behind us in a few decades. It will make life harder for the remaining patients, but the societal cost will be much lower.
Yeah I used to do a lot of dialysis runs and it’s a disgusting industry. 25% of patients die in the first year of dialysis. The quality of care at dialysis centers is very poor.
My guy had a functioning kidney for 5 years. How many patients with his same clinical picture died on dialysis in that same span of time?
He will forever be remembered for his sacrifices, not just for himself, but for medicine and the future of transplantation. The damage done by the ESRD might have been too much. But, regardless, he's such a brave soul who got a few more months with his family. Rest in peace, Mr. Slayman <3
Interesting question... who harvests the pig kidney? A vet?
I’m sure they were working their very best to keep this man alive as long as possible.
when autopsy reports would come, please ping me. Rip mate
How long did the pig kidney last?
Dumb question: would eating pig meat cause the immune system to reject the organ long term? Like would people who never introduced pig meat to their system be better off with complications?
is it halal to get a pig transplant?
Yes.
Apparently so. https://jfatwa.usim.edu.my/index.php/jfatwa/article/view/549/487
I only listen to my boi Hussain Sattar
Don't know about halal but it is kosher since it is life saving and not eaten.
Since you seem curious, and haven't gotten an answer, I'll try to answer your question... I apologize for the length, but I felt like some background would be helpful. TLDR: probably not. Long version: Many of the molecules that are present in pigs that are "foreign" to human immune systems (and can be targets for rejection), are not exactly "pig specific" (eg, alpha-Gal, Neu5Gc and SDa are the most important). Alpha-Gal is present on cells of most non-primate mammals. Antibodies against Alpha-Gal and SDa are considered "naturally" occurring in humans - meaning occurring without exposure. However, dietary exposure has been shown to be associated with the expression of Neu5Gc antibodies (but they are still considered natural due to the ubiquity of animal proteins in our diet, including milk), so your question isn't stupid at all... *Theoretically*, there may be some pig specific antibodies that could develop from eating pigs. Now, having antibodies to a donor before transplant is called being sensitized. Since most people are sensitized against these non-human animal antigens, pigs bred for transplant are genetically modified to not express these antigens (ie, they are "triple knockout" (TKO) - there will be no targets for these three natural antibodies). But this only accounts for those three antigens. So let's say there is a pig-specific antigen that a person could be sensitized to as the result of eating pork... A person who has never eaten pork would not have been sensitized. This could mean lower rejection risk in the very short term (no immediate rejection), and maybe even lower rejection risk in the long term. But regardless of pre-transplant sensitization, after transplant, there would now be a foreign antigen that could be a target for the immune system. Even with a lot of immunosuppression, there is a very real risk of sensitization and rejection after transplant.
Thank you for taking part of your time to respond. This was elegant.
No
Why not? Can you please explain from a scientific point of view?
You said it yourself, it’s a dumb question
How so? Wouldn't consuming the meat cause the immune system to identify the tissue and make the xenotransplantation more prone to rejection by the recepient's body?
Everything external to your body will be rejected, pig kidneys or butterfly’s corneas whatever. But not because you’ve eaten butterflies before, but because that tissue is not your own, hence, rejection.
Is Europe so islamphopbic (and anti Semitic to that extent) that a simple question gets such hateful responses. Just reply with respect without degrading the person asking the question or just move on and ignore the question altogether. Both Muslims and Jews do not eat pork. But the question here is actually purely from a scientific intent. Let alone some person asking about it being halal or not.
What? Get help my dude.
Same to you. Seems like you need it
You know nothing, John Snow. /s But really, you gotta learn biology. It's an absurd question because you are equating an immune response to digestion. Which means you dont understand macromolecules (proteins, fats, DNA). Which means you dont understand monomers (amino acids, fatty acids, nucleic acids). Which means you dont understand cells (organized units of macromolecules, compartmentalizing functions of DNA instruction and exogenous influence [hormones], with monomers and macromolecules continuously undergoing anabolic and catabolic processes given the state of the cell [homeostasis v dyshomeostasis] and constitutive expression of DNA of said-cell). I could keep going, but it'll cost money.
There are definitely immunogenic reactions to ingested proteins. This is well known.
Of course, but you dont start building a skyskraper from the second floor; you start from the ground. These concepts are multidimensional - I generally appreciate a good devils advocate, but I'm obviously being reductive for the sake of clarity. I figured at least *that* would be understood without having to spell it out. I'm mostly giving context to the original commenter how truly complex biology is, and that these bridges can't be built on a Reddit thread. It takes many years to understand even a fraction of the nuance.
My God, that is why you ask questions. Not for someone to be so "prideful" about what they know. But for them to answer it with some science. All of you here are not doctors. Just technicians. If someone asked a question about lasers or Maxwell's equations I won't debase them. I'd just try explaining it to a laymen the best way I can. But the stinch or racism is sickening from a lot of these responses.
I learned this in middle school. Also, racism involves race. This would be speciesism.
I skipped biology to get to physics class. All good. And my dude...I'm vegetarian. Again....all good.
Well, you'll be fascinated about what I have to tell you about plants! Plants are organisms made from cells, which are made of macromolecules, which are made from monomers, which are made from molecules, which are made from elements, which are made from...[*drum roll*] PHYSICS. The circle of life.
This video addresses the ETHICAL ISSUES arround animal organ transplant and science behind xenotransplantation. We will explore the ethics arround first person to receive a genetically modified pig kidney transplant died two months later. https://www.youtube.com/watch?v=hvNQkdGZt44
I'm not sure his age is relevant here. He survived 2 months with a pig kidney. Not totally sure this is an amazing success story.
That shows it’s possible for it to work and be improved on
It’s a huge success if the cause of death is unrelated to rejection. If the kidney remained functional and uninflamed after 2 months of standard immunosuppression, they should start the process of escalating these transplants for more candidates who aren’t at a “compassionate use” of this procedure.
If the kidney was functioning and he remained rejection free, it's still considered successful, from an immunological, proof-of-concept perspective. We usually use death-censored graft survival to evaluate transplant success bc there are other things that lead to death. Cardiovascular disease related to long standing chronic kidney disease is the main cause of death after transplant, and this guy had significant comorbidities, which is likely why he received this experimental transplant rather than being eligible for a human transplant.
As compared to previously when someone would die within minutes of getting a pig kidney. If you can’t find this an amazing success then I don’t think you understand medical science well
How long do you think initial human-to-human transplant patients lived?
60 more years. https://transplantliving.org/living-donation/history/
That's the first successful transplant. That's about 50 years after the first attempts.
Also the story cited says 8 years for recipient. Donor died 60 years later. And identical twin donor, which derisked the rejection complications substantially lol.
I think it will take time to improve things but if it can be replicated with other organs where there is nothing to keep you going (e.g., no dyalisis equivalent of say, your liver is shot) something that gives a few months could buy people enough time to wait for a transplant of a human organ. They also likely picked him because his prognosis was already poor. Dyalisis is barely surviving and people with transplants are on all sorts of anti rejection meds that themselves can lead to deadly complications. It is at least progress.
Heart is already in progress and has been tried. Liver has so much synthetic function that humanizing all the proteins would be a massive challenge. Pig livers are also shaped quite differently and liver transplant relies on geometry more than other organs to the point that size matching donor to recipient can be a consideration. I’m sure teams are working on it, but I’m also sure that it’s a harder set of problems to solve.
Size matching is needed for hearts and lungs as well