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

Robert A. Montgomery(MACOM (United States)), Jeffrey Stern(MACOM (United States)), Bonnie E. Lonze(MACOM (United States)), Vasishta Tatapudi(MACOM (United States)), Massimo Mangiola(MACOM (United States)), Ming Wu(MACOM (United States)), Elaina Weldon(MACOM (United States)), Nikki Lawson(MACOM (United States)), Cecilia Deterville(MACOM (United States)), Rebecca A. Dieter(MACOM (United States)), Brigitte Sullivan(MACOM (United States)), Gabriella Boulton(MACOM (United States)), Brendan Parent(MACOM (United States)), Greta L. Piper(MACOM (United States)), P. Sommer(MACOM (United States)), Samantha Cawthon(MACOM (United States)), Erin M. Duggan(MACOM (United States)), David Ayares(MACOM (United States)), Amy Dandro(MACOM (United States)), Ana Fazio-Kroll(MACOM (United States)), Maria Kokkinaki(MACOM (United States)), Lars Burdorf(MACOM (United States)), Marc I. Lorber(MACOM (United States)), Jef D. Boeke(MACOM (United States)), Harvey I. Pass(MACOM (United States)), Brendan J. Keating(MACOM (United States)), Adam Griesemer(MACOM (United States)), Nicole Ali(MACOM (United States)), Sameer Mehta(MACOM (United States)), Zoe A. Stewart(MACOM (United States))
New England Journal of Medicine
May 18, 2022
Cited by 462Open Access
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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: 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.).


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