The progress that has been made in transplantology is gigantic
Every year on 26 January we celebrate the National Transplant Day. It is the anniversary of the first successful kidney transplant, which took place at our university in 1966. What do we know about it?
Prof. Maciej Kosieradzki: The transplantation was performed by a team of surgeons led by Prof. Jan Nielubowicz. The operation was attended, among others, by Prof. Jerzy Szczerbań, Prof. Waldemar Olszewski and Prof. Wojciech Rowiński. The patient, a kidney recipient, was prepared and cared for after the surgery by Prof. Tadeusz Orłowski and his team. This procedure is considered a milestone in the development of transplantology. Although it was not the first kidney transplant in Poland (the first was performed by Prof. Wiktor Bross from Wrocław) - it was the first successful one. The recipient, a young girl, a nursing student, lived another 9 months after the procedure. She died of pancreatitis. During this time, she functioned with a working kidney, preserved diuresis and reasonably normal creatinine levels. Dialysis-free. We consider it a great success of that time.
What made the surgery under the direction of Prof. Nielubowicz successful?
M.K.: We have never analyzed it in detail. Today, the source documents can no longer be accessed. However, it must be emphasized that our surgeons drew on the experience of their foreign colleagues, which was not easy in those days. After all, we were living behind the Iron Curtain, and yet virtually all of the surgeons involved in this procedure had taken part in training abroad. For example, Prof. Rowinski was fresh from a residency in Boston, where he stayed for several years and worked with the team that was the first in the world to perform a successful kidney transplant. It is also worth noting that in those days the organ harvesting itself was a major challenge. Today, in 95 percent of cases, we retrieve organs from people who have died of brain death. The remaining 5 percent are transplants involving living donors. Brain death is a condition when the heart is beating and a ventilator is breathing for the person. Therefore, we have time, sometimes several hours, sometimes tens of hours, to organize the donation. However, the Harvard criteria defining brain death did not appear until 1968. So in 1966 it could not be diagnosed at all. Of course, anesthesiologists were able to identify patients for whom nothing more could have been done. However, organs were not allowed to be retrieved from them until cardiac arrest had occurred. So, before Professor Nielubowicz performed the first successful transplant, the patient was waiting in the hospital for the procedure, and the surgeons were waiting for another patient in a very serious condition to go into cardiac arrest. When it did occur, a so-called "quick donation" was performed. These were the beginnings of Polish transplantology. What is interesting, today we are preparing for taking organs after cardiac arrest again. There are logistical, organizational, and legal barriers. However, I think this method has a lot of potential. In Spain, which is the best organized country when it comes to the donation system, more than 10 donors per million inhabitants are donors after irreversible cardiac arrest.
What is the current situation in Polish transplantology?
M.K.: The past two years have been very difficult for us. Burdening the ICUs with the extra work of treating COVID-19 patients is not conducive to organ procurement. There are times when the entire intensive care unit is occupied with covid patients. We do not take organs from such people for fear of transmitting infection. Besides, these patients usually die of multiple organ failure, so they cannot be donors.
How many transplants are performed annually?
M.K.: Before the pandemic we had 1300 -1500 organ transplants in Poland per year. The majority of them were kidney transplants - up to 1150 per year. As far as the liver is concerned, we performed an average of 350 procedures. In the pandemic, the number of transplants of these organs declined sharply. Fortunately, the unfavorable trend does not apply to the heart. Last year we transplanted the most hearts in Poland throughout history. The lung transplant program is also growing very well. We do not do heart or lung transplants at our university yet. This may change due to the transfer of Associate Professor Bartosz Kubisa and Prof. Mariusz Kuśmierczyk to MUW.
Thus, it can be seen that the progress which has been made in transplantation since the 1970s has been enormous....
M.K.: Gigantic. Today we are able to undertake transplants that no one would have attempted them several years ago. One example is a simultaneous liver and pancreas transplant. This was done by Prof. Wojciech Lisik and Marek Pacholczyk, MD, PhD, from the Department of General and Transplantation Surgery of the Medical University of Warsaw. Earlier, Prof. Krzysztof Zieniewicz and Prof. Mariusz Kuśmierczyk at the National Institute of Cardiology in Anin transplanted a heart and liver simultaneously. And at the Silesian Center for Heart Diseases in Zabrze, a lung and liver transplant were performed at the same time. These are extremely complex, difficult and extensive procedures that few centers in the world decide to perform.
In what direction will transplantation evolve?
M.K.: Now reports of xenotransplants, or transplants of organs from animals, are sweeping the world. Let me remind you that the idea is not new. In the 1980s, doctors from Loma Linda University Medical Center in California, under the direction of Dr. Leonard Bailey, decided to implant a baboon heart in a girl. The little patient survived only 21 days. After this failure, the scientific community turned away from xenotransplantation. Now the idea is coming back, except that the organ donors are pigs. It turns out that this animal is the optimal model when it comes to organ transplants. Its kidneys, liver, heart and lungs are similar in size to organs in an adult human. The problem, however, is that xenografts require powerful immunosuppression. We humans (more broadly, primates) do not have an enzyme called alpha-galactosyltransferase (N-GAL gene) on our cell surface, which is found in the tissues of other mammals. And it is the most powerful immunizing antigen. It causes organs from other mammals to be immediately recognized by the human body and rejected.
And how are scientists trying to solve this problem?
M.K.: Modern biotechnology methods come to the rescue. Scientists use a technique commonly called molecular scissors. It is an arrangement of enzymes that are used to cut out a specific gene. This allows to cut the DNA anywhere and remove the chosen gene. In this way, you can get a pig with a modified genome that minimizes the risk of transplant rejection. Then it is enough to clone such an animal. The Institute of Zootechnics in Cracow and the Polish Academy of Sciences in Poznań have bred a pig that can be an organ donor. The animal does not have the N-GAL gene deleted, just a human gene added that masks the antigenicity of the cells. The human gene was inserted using a virus particle. Currently, more than 100 pigs with such modification have already been created. Their skin is used in the Burn Treatment Center in Siemianowice Śląskie as material for dressings for burned people. However, the animals are still far from being used as kidney or heart donors in Poland.
Has there been any xenografting done in the world in recent years?
M.K.: Two such procedures were performed last year. The first took place in New York - it was a kidney transplant. The recipient was a person who died of brain death. This woman had previously signed a declaration that she wanted to become an organ donor. However, due to medical reasons, this proved impossible. So the doctors asked the family if, in the situation of brain death in their relative, they would agree to a certain experiment. After obtaining consent, they sewed a kidney derived from a transgenic pig into the patient's femoral vessels. The organ was outside, so it was possible to observe whether it was being rejected and if it has normal diuresis. It is interesting to note that the pig that was the kidney donor was registered with the FDA as a food producing animal. It was deprived of the N-GAL gene so that meat from it could be eaten by people allergic to the alpha-galactosyltransferase enzyme. The second xenograft procedure was performed earlier this year in Maryland. Heart transplantation was performed in a 57-year-old patient who gave informed consent. The donor was a transgenic pig in which not only the N-GAL gene but four others were removed. The patient is still alive today.
Xenografts are controversial, who might this method be for?
M.K.: Considering all the risks associated with xenografts, it would be best to perform them in situations where there are no other alternatives. This means that a patient needs a transplant immediately but cannot wait for an organ from a deceased person. The problem, however, is that these potential recipients of zoonotic organs are in very serious condition, usually without contact, so they cannot consent to such a procedure.