Xenotransplantation of a Porcine Kidney for End-Stage Kidney Disease

Tatsuo Kawai(Harvard University), Winfred W. Williams(Harvard University), Nahel Elias(Harvard University), Jay A. Fishman(Harvard University), Kerry Crisalli(Harvard University), Alban Longchamp(Harvard University), Ivy A. Rosales(Harvard University), Michael W. Duggan(Harvard University), Shoko Kimura(Harvard University), Leela Morená(Harvard University), Thiago J. Borges(Harvard University), Toshihide Tomosugi(Harvard University), Ahmad Karadagi(Harvard University), Tsukasa Nakamura(Harvard University), Kassem Safa(Harvard University), Alessia Giarraputo(Harvard University), Claire Avillach(Harvard University), Eva Patalas(Harvard University), R. Neal Smith(Harvard University), David H. Sachs(Harvard University), A. Benedict Cosimi(Harvard University), Joren C. Madsen(Harvard University), David K.C. Cooper(Harvard University), Richard N. Pierson(Harvard University), Steve Perrin, R. Anand(Genesis Foundation), Sagar Chhangawala(Genesis Foundation), Matthew Coscarella(Genesis Foundation), Alexandre Daigneault(Genesis Foundation), Feng Li(Genesis Foundation), Owen Pearce(Genesis Foundation), Wenning Qin(Genesis Foundation), William T. Serkin(Genesis Foundation), Ming Wai Yeung(Genesis Foundation), Kristen Getchell(Genesis Foundation), Susan C. Low(Genesis Foundation), Michael A. Curtis(Genesis Foundation), Robert B. Colvin(Harvard University), Leonardo V. Riella(Harvard University)
New England Journal of Medicine
February 7, 2025
10.1056/nejmoa2412747
Cited by 126

Abstract

Xenotransplantation offers a potential solution to the organ shortage crisis. A 62-year-old hemodialysis-dependent man with long-standing diabetes, advanced vasculopathy, and marked dialysis-access challenges received a gene-edited porcine kidney with 69 genomic edits, including deletion of three glycan antigens, inactivation of porcine endogenous retroviruses, and insertion of seven human transgenes. The xenograft functioned immediately. The patient's creatinine levels decreased promptly and progressively, and dialysis was no longer needed. After a T-cell-mediated rejection episode on day 8, intensified immunosuppression reversed rejection. Despite sustained kidney function, the patient died from unexpected, sudden cardiac causes on day 52; autopsy revealed severe coronary artery disease and ventricular scarring without evident xenograft rejection. (Funded by Massachusetts General Hospital and eGenesis.).

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