Robert A. Montgomery; Jeffrey Stern; Bonnie E. Lonze; Vasishta Tatapudi; Massimo Mangiola; Ming Wu; Elaina Weldon; Nikki Lawson; Cecilia Deterville; Rebecca A. Dieter; Brigitte Sullivan; Gabriella Boulton; Brendan Parent; Greta L. Piper; P. Sommer; Samantha Cawthon; Erin M. Duggan; David Ayares; Amy Dandro; Ana Fazio-Kroll; Maria Kokkinaki; Lars Burdorf; Marc I. Lorber; Jef D. Boeke; Harvey I. Pass; Brendan J. Keating; Adam Griesemer; Nicole Ali; Sameer Mehta; Zoe A. Stewart · 2022 · New England Journal of Medicine
Paper
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.).
Analysis
This study reports on two cases of pig-to-human kidney xenotransplantation using genetically modified porcine kidneys, demonstrating successful short-term function and absence of hyperacute rejection in brain-dead human recipients.
Discovery
Liu WB; Rui HL; Liu BL
Denner J
He Y; Peng Y; Liu Y; Jia J; Li L; Hara H; Feng S; Pan Z
Mulbjerg H; Ringgaard S; Agger P
Rao JS; Rangarajan P; Shetty A; Steinhoff M; Tran A; Crane AT; Low WC; Steer CJ; Ramachandran S
Bartley P. Griffith; Corbin E. Goerlich; Avneesh K. Singh; Martine Rothblatt; Christine L. Lau; Aakash Shah; Marc I. Lorber; Alison Grazioli; Kapil Saharia; Susie N. Hong; Susan Joseph; David Ayares; Muhammad M. Mohiuddin
Source record