When did the transplant occur?
Saturday, March 16, 2024.
How long did the procedure take?
Approximately four hours.
How many surgeons were on the team?
Five surgeons.
How many caregivers?
The kidney transplant team includes a transplant surgeon, a transplant nephrologist, a nurse practitioner, a transplant infectious disease expert, a social worker, a nutritionist, a nurse, and a pharmacist.
The patient has been attended to by 2-3 nurses daily during his stays in the ICU and the inpatient transplant unit.
How will the transplanted organ function?
We expect the xeno-kidney transplant to function very similar to a human kidney, maintaining the body’s water and mineral balance, and excreting waste in the urine.
How did the patient come to need a transplant?
The patient developed kidney failure due to Type 2 diabetes mellitus and hypertension.
How old is the patient?
62 years old.
What information can you provide about the patient?
The patient’s name is Mr. Richard Slayman. He is a resident of Weymouth, Mass.
What is xenotransplantation?
Xenotransplantation is transplanting organs or cells from a species other than humans into humans. In this case, kidneys from genetically modified pigs are being evaluated to try to ease the significant shortage of human organs available for kidney transplantation. If pig kidneys can perform better than dialysis, pig kidney xenotransplantation could become a new way to provide a potentially readily available source of donor organs, offering new hope to those waiting for life-saving transplants.
How does xenotransplantation work?
Genetically modified pigs have been developed to increase their compatibility with humans. Pigs intended as organ donors for humans are grown in isolation under special conditions to prevent the pig from being exposed to infections that might harm the human recipient of that pig’s organs. These special pigs have organs of similar size and function to human organs. The genetic modifications of these pigs have also made them more compatible with humans.
What is compassionate use?
It is a regulatory pathway that allows patients with serious or life-threatening conditions to access experimental therapies that have not yet been approved by the FDA. Despite not being approved, these therapies are subject to strict criteria and oversight to minimize risks to patients and to gather additional data on the experimental treatment's safety and effectiveness.
How will success be defined with this transplant?
Success will be defined by the absence of dialysis requirement for the patient. We will be monitoring his kidney function through blood and urine tests in addition to regular physical exams.
What type of follow-up care can the patient expect?
The patient will be followed like other kidney transplant patients with twice weekly labs and clinic visits for the first month post-transplant followed by weekly for the subsequent month. Spacing of visits and labs will occur following that depending on his clinical course.
What is the risk of rejection?
Rejection is always a concern in any organ transplant, as the immune system is capable of recognizing the organ as a threat. As this is the first time a xeno-kidney is transplanted into humans, we don’t know what the risk of rejection is, but it is expected that with the use of a combination of medications to weaken the immune system, the risk will be significantly reduced.
What sorts of medications/therapies will be involved to decrease the levels of rejection?
Like human kidney transplantation, immunosuppressive drugs are crucial to prevent the rejection of the xenotransplant. Immunosuppressive medications help suppress the function of immune cells that are responsible for rejecting a transplanted organ. In xenotransplantation, a newer immunosuppressive drug is used in combination with some of the drugs that recipients of human kidney transplants take to protect against rejection of the transplanted organ. The specific drug regimen is based on results of experiments in pig-to-non-human primates.
Are there incompatibilities between the human body and the pig kidney?
Yes. The usual ‘farm’ pig carries quite a few incompatibilities that prevent it from working normally in the human body. However, recent genetic engineering advances have helped scientists make the pig organs more ‘compatible’ with human beings (Figure). In terms of kidney function, the genetically engineered pig kidney is capable of performing all the essential functions of a normal human kidney, such as maintaining water and mineral balance, and excreting waste. In addition, other genetic modifications in the special pigs have been made to minimize the risk of inappropriate blood clotting in the pig kidney, and to decrease inflammation in the pig kidney. It is possible that patients receiving a xeno-kidney may be required to take a hormone called erythropoietin to support red blood cell production and prevent anemia.
Figure 1. Illustration of the genetic modifications of humanized pigs and their potential impact on the xeno-immune response.
What are the qualifications and experience of the MGH researchers in xenotransplantation?
MGH has been a leader in xenotransplantation for more than 30 years. Our scientists have conducted extensive research in non-human primates. This experience has allowed us to develop critical expertise in the surgical techniques of implanting xenografts, the diagnostic approaches to detect xeno-related problems, and the anti-rejection regimen that we believe will be most likely to prevent pig kidney rejection.
What is the risk of infection to the patient after xenotransplantation?
Infections are common after transplantation due to the requirement of anti-rejection medications that weaken the entire immune system. This risk is increased in all transplant patients, regardless of the source of the donor organ (human or pig). The MGH staff is experienced in caring for infections after transplantation.
How was this procedure developed?
Mass General Transplant Center physicians started with discussions about the current procedure more than a year ago but worked intensively for six months with weekly meetings in order to develop the most successful protocol possible.
How long did it take for review and approval?
The FDA was extremely efficient in their evaluation process. Prior to submitting our application, Mass General Transplant Center physicians had multiple exchanges with the FDA for over twelve months in order to understand all the required documents for the initial submission. Once the FDA received the application, Transplant Center physicians had regular meetings with the FDA team to discuss specific concerns. We also received multiple FDA communications per week with additional requests for clarification prior to approval. The final protocol was significantly improved after all their feedback and suggestions.
How was the patient selected and approached?
Mass General Transplant Center physicians started screening patients from our waiting list in January 2023. We have also conducted multiple meetings with treating nephrologists to help identify the ideal candidate.
Is this the first-of-its-kind transplant to be conducted?
Yes. This is the first transplant of a genetically modified pig kidney into a living human in the world. Other hospitals in the U.S. have transplanted genetically modified pig kidneys into deceased humans following brain death to assess their viability in humans, but this the first in a living patient.
How is this transplant different than the pig heart transplants performed in Maryland?
Our patient is healthier than the two recipients of the pig heart transplants. Our research shows that kidneys do better than hearts.
How long do you anticipate the patient being under observation before being discharged from the hospital?
The patient will be observed in the hospital for at least one week prior to discharging him home.
Can you briefly explain how the organ was transplanted and the procedure itself?
The pig kidney used in the transplant was comparable in size to a human kidney. The left kidney was transplanted into the left lower abdomen, following the standard procedure for human kidney transplantation. However, due to the patient's severe vascular disease, the transplant procedure posed additional challenges. Despite this, the kidney's artery and vein were successfully connected to the recipient's artery and vein in the left lower abdomen. Subsequently, the ureter was joined to the patient's bladder.
Are there any risks to the patient of infections typically carried by pigs?
All potential porcine pathogens are closely monitored under strict FDA guidance. It's worth noting that similar transplants using nonhuman primates have been conducted for several decades at MGH and other facilities as part of preclinical studies. Importantly, no pig-derived infectious diseases have been detected in any individual involved in these studies. Nonetheless, we remain vigilant and will meticulously monitor for any signs of infectious diseases.
What other outside organizations were involved?
eGenesis of Cambridge, Mass. supplied the genetically edited pig kidney. Alexion Pharmaceuticals, Inc. of Boston and Eledon Pharmaceuticals, Inc., of Irvine, Calif. provided the novel immunosuppressant drugs the patient is receiving.
Individuals concerned with the welfare of animals have expressed their discomfort with xenotransplantation. How can you address their concerns?
MGH acknowledges the essential role that animals play in allowing researchers to make discoveries that turn into diagnostics and treatments that cure diseases and improve quality of life. We are committed to ensuring the highest ethical standards of animal care and use at MGH and believe that animals used in biomedical research deserve the best possible treatment and care. Fortunately, good animal welfare and care directly strengthens scientific rigor, and better animal welfare is often aligned with better scientific results.
Pig-to-human xenografting is the most promising solution currently available to address the chronic shortage of donor organs available for clinical transplantation. The advent of pigs that are born and raised under defined, highly regulated, pristine conditions and that are genetically modified, and purpose-bred and raised to reduce the potential for rejection and other clinical complications makes survival a reality for patients with few other options.
What is the ideal candidate profile for this type of transplant?
There are many debates in the field about who is the ideal candidate for xenotransplantation. Overall, patients that have been doing poorly on dialysis with a significant impact on their quality of life and have a long-waiting time for a transplant could be good candidates for a xenotransplant.
How is this procedure being paid for? Will the patient’s insurance cover it?
This procedure was supported in part by eGenesis and MGH. As further clinical research studies are conducted to demonstrate the success of xenotransplantation in humans, we hope that insurance will eventually cover for this cost in the future.
For current and prospective patients interested in more information about xenotransplantation at MGH, please visit www.mghxenotransplant.org.
