24 January 2022

Pork kidneys

More than 800,000 Americans live with kidney failure, most of them do not even get on the waiting list for donor organs. The hemodialysis procedure helps to maintain life for some time, while transplantation provides a better quality of life and increases survival for the few people to whom it is available. Waiting for a donor can last up to five years, and in some cases it is approaching 10 years. Almost 5,000 people a year die waiting for a kidney transplant.

Researchers from the University of Alabama at Birmingham have reported the first successful transplant of genetically modified pig kidneys to a person with brain death. Before that, the recipient's own kidneys were removed, and organs for transplantation were obtained from a genetically modified pig free of specific pathogens.

Gene editing to reduce the risk of immune rejection has made it possible to transplant organs from pigs to humans, potentially useful for thousands of patients who face organ failure, disease or injury. Genetically modified pig kidneys have been repeatedly tested on non-human primates; a new human study may provide important information about the potential safety and effectiveness of xenotransplantation of kidneys in humans. The success of the study gives hope for solving the problem of the shortage of donor organs with the help of xenotransplantation.

In this study, for xenotransplantation, kidneys were removed from a donor pig placed in a pathogen-free environment. They were then stored, transported and processed in the same way as human kidneys. Before the operation, the recipient with brain death and the donor animal underwent a compatibility test to determine whether the genetically modified pig kidneys and their intended recipient were well combined. A similar comparison is carried out with each human-to-human kidney transplant; however, this pig-human tissue matching test was developed at the University of Alabama and was the first time that a match between different species was confirmed.

Pig kidneys during transplantation were placed in the anatomical area used for transplantation from human donors, with the same technique of suturing to the renal artery, renal vein and ureter. The brain-dead recipient received standard immunosuppressive therapy used after human-to-human kidney transplantation.

Hyper-acute rejection was not observed, and the kidneys remained viable until the termination of the study – 74 hours. No chimerism or transmission of pig retroviruses was detected. Longitudinal biopsy revealed no signs of cellular rejection, deposition of antibodies or complement proteins. Xenografts released different amounts of urine, but creatinine clearance was not restored. Whether brain death and/or damage to microvessels affected this remains unknown. 

The authors received the consent of the relatives of the study participant Jim Parsons, the approval of the Independent Ethical Committee (Institutional review board, IRB) and the Committee for the Care and Use of Animals (Institutional Animal Care and Use Committees, IACUC). The study was conducted in accordance with standards directly comparable to those that will be applied for the Phase 1 clinical trial.

Article by P.M.Porrett et al. First clinical-grade porcine kidney xenotransplant using a human decedent model is published in the American Journal of Transplantation.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on materials from the University of Alabama at Birmingham: UAB announces first clinical-grade transplant of gene-edited pig kids into brain-dead human.


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