Results of Two Cases of Pig-to-Human Kidney Xenotransplantation

Robert A. Montgomery, Jeffrey M. Stern, Bonnie E. Lonze, Vasishta S. Tatapudi, Massimo Mangiola, Ming Wu, Elaina Weldon, Nikki Lawson, Cecilia Deterville, Rebecca A. Dieter, Brigitte Sullivan, Gabriella Boulton, Brendan Parent, Brendan Parent, Philip Sommer, Samantha Cawthon, Erin Duggan, David Ayares, Amy Dandro, Ana Fazio-KrollMaria Kokkinaki, Lars Burdorf, Marc Lorber, Jef D. Boeke, Harvey Pass, Brendan Keating, Adam Griesemer, Nicole M. Ali, Sapna A. Mehta, Zoe A. Stewart

    Research output: Contribution to journalArticlepeer-review

    Abstract

    BACKGROUND Xenografts from genetically modified pigs have become one of the most promising solutions to the dearth of human organs available for transplantation. The challenge in this model has been hyperacute rejection. To avoid this, pigs have been bred with a knockout of the alpha-1,3-galactosyltransferase gene and with subcapsular autologous thymic tissue. METHODS We transplanted kidneys from these genetically modified pigs into two brain-dead human recipients whose circulatory and respiratory activity was maintained on ventilators for the duration of the study. We performed serial biopsies and monitored the urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection. RESULTS The xenograft in both recipients began to make urine within moments after reperfusion. Over the 54-hour study, the kinetic eGFR increased from 23 ml per minute per 1.73 m2 of body-surface area before transplantation to 62 ml per minute per 1.73 m2 after transplantation in Recipient 1 and from 55 to 109 ml per minute per 1.73 m2 in Recipient 2. In both recipients, the creatinine level, which had been at a steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in Recipient 1 and from 1.10 to 0.57 mg per deciliter in Recipient 2. The transplanted kidneys remained pink and well-perfused, continuing to make urine throughout the study. Biopsies that were performed at 6, 24, 48, and 54 hours revealed no signs of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with the native kidneys. CONCLUSIONS Genetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. (Funded by Lung Biotechnology.

    Original languageEnglish (US)
    Pages (from-to)1889-1898
    Number of pages10
    JournalNew England Journal of Medicine
    Volume386
    Issue number20
    DOIs
    StatePublished - May 19 2022

    ASJC Scopus subject areas

    • Medicine(all)

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