A successful double pig kidney transplant was carried out on a brain dead patient.

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This experiment aimed to determine whether organ transplants of this type are safe before putting them through clinical trials.

It was discovered that the genetically engineered pig's kidneys could produce urine and were not rejected by the human recipient during the days-long trial.

One brain-dead patient was used as a test subject. The family of that patient gave their consent, according to the new report published in the American Journal of Transplantation this past Thursday (Jan. 20). Before conducting official clinical trials, the study team wanted to answer a few important safety questions before attempting to transplant pig kidneys into living individuals.

This was addressed in the organ recipient, who was closely monitored for any signs of transplant rejection, viral transfer from the pig donor, or surgical issues specific to the pig-to-human operation. They found nothing. The study authors write in their report, "This strategy is premised on the idea that such concerns must be answered before clinical trials of efficacy can be responsible."

Live Science previously revealed that in September of 2021, researchers at NYU Langone Health performed a similar experiment with a brain-dead patient and implanted a genetically modified pig kidney in the patient. As long as the kidney functioned normally for 54 hours, there were no immediate signals of rejection, according to the NYU team that conducted the study. However, the kidney remained attached to blood arteries in the recipient's upper leg throughout the trial.

Only one kidney is transplanted into the recipient's body during a human-to-human transplant. Still, in this study, in an email to Live Science, two pig kidneys were used, according to Dr. Jayme Locke, director of the Comprehensive Transplant Institute and lead surgeon at the UAB Department of Surgery. Using the identical pig kidneys that would be used in a future clinical trial, Locke said the team followed the same approach from procurement to surgery.

Revivicor, a United Therapeutics affiliate, provided the genetically modified pig utilized in the research, whose kidneys were used in the experiment. (Several Revivicor workers, including the company's chief scientific officer, are co-authors of the current research.) According to the New York Times, doctors performed a groundbreaking heart transplant earlier this month with the help of the same genetic modifications as the pig used in the new kidney transplant study; this pig had the same genetic modifications as the pig used in the new kidney transplant study.

It is hoped that these genetic alterations will lower the chance of rejection by the human body. Genes that code for specific carbs, for example, can trigger an aggressive immunological response in the human body, which is why the pigs have been genetically engineered. Additionally, the pigs' organs should cease developing when transplanted into humans since they lack a gene that codes for a certain growth hormone receptor.

Last but not least, the pigs have been genetically modified to include six human genes: four to enable the immune system to recognize each pig's organs and two to prevent blood clots from forming.

Before returning the kidneys to the animal, the researchers examined them. According to the researchers, the pigs' kidneys closely resembled human kidneys, but there were some differences.

Although the kidneys were soft to the touch, their outer surfaces were covered with an even thinned capsule; the width of the urinary tracts, which carry urine from the kidney to the bladder, was significantly greater in the pigs than in humans. Although it's not apparent whether these small variations affect kidney function in humans, the study's authors remark in their paper that "these discoveries underlined the necessity for precise handling and surgical approach."

To lessen the likelihood of organ rejection, the transplant team removed both of the human recipient's kidneys and administered immunosuppressive medicines. Once the kidneys had been transplanted, the researchers kept three days of observation in mind.

They noticed that the body's immune system was not responding to the kidney at the time. Antibodies in the blood can cause "hyperacute rejection," in which the body begins attacking a transplanted organ as soon as it's connected to a human circulatory system. No porcine endogenous retroviruses were found in the donor pig after the transplant, and the researchers were certain that the pig's DNA was free of these viruses as well.

The right kidney originally produced "robust" pee after transplantation, whereas the left produced significantly less urine. According to the scientists' findings, the explanation for this discrepancy is unknown but may be connected to the initial method used to obtain each organ from the donor pig. After the pig's blood supply was cut off and before the kidney was placed on ice, the left one remained at room temperature longer than the right one. The authors concluded that more research is needed to learn more about how these characteristics might affect a pig organ's performance in a human recipient.

Even though both kidneys excreted urine, they could not perform the functions of a fully-functioning kidney. As a waste product of muscle cell function, creatinine was shown to remain constant in the circulation and to be expelled insignificantly by either kidney. Researchers aren't sure if this impairment was caused by renal damage or the physiological changes after brain death.

According to Locke, "the brain death environment is highly hostile, measuring kidney function challenging. Organs began to fail, aberrant blood coagulation developed, and his blood grew more acidic due to the buildup of hydrogen ions during the experiment. Authors claimed that despite using numerous drugs and infusions to counteract the consequences of brain death, it is possible that these effects negatively impacted the pig kidney's function.

According to Locke, in human-to-human transplantation, kidneys from brain-dead donors generally exhibit delayed graft function, meaning they don't produce urine right away and take several extra weeks to clear creatinine.

The study's authors concluded that while many obstacles to pig-to-human kidney transplants have been overcome, many questions concerning the operation remain unsolved. These problems may be answered by future research in brain-dead persons, while others may necessitate a study in monkeys. Clinical studies involving real people will also be used to answer some of these problems in the future.

An Investigational New Drug Application (INDA) has been submitted to the FDA by Locke and her colleagues. It will allow them to conduct a clinical trial using kidneys that have been genetically edited. They will also have to get the go-ahead from UAB's Institutional Review Board to conduct such a study. There are "well underway" Locke's comments on the two initiatives.

Reference : https://www.livescience.com/double-pig-kidney-transplant-experiment

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