Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs

Daniel Eisenson, Yu Hisadome, Michelle Santillan, Hayato Iwase, WeiLi Chen, Akira Shimizu, Alex Schulick, Du Gu, Armaan Akbar, Alice Zhou, Kristy Koenig, Kasinath Kuravi, Farzana Rahman, Lori Sorrells, Lars Burdorf, Kristina DeSmet, Daniel Warren, Leigh Peterson, Marc Lorber, David Ayares, Andrew Cameron and Kazuhiko Yamada ()
Additional contact information
Daniel Eisenson: The Johns Hopkins School of Medicine
Yu Hisadome: The Johns Hopkins School of Medicine
Michelle Santillan: The Johns Hopkins School of Medicine
Hayato Iwase: The Johns Hopkins School of Medicine
WeiLi Chen: The Johns Hopkins School of Medicine
Akira Shimizu: Nippon Medical School
Alex Schulick: The Johns Hopkins School of Medicine
Du Gu: The Johns Hopkins School of Medicine
Armaan Akbar: The Johns Hopkins School of Medicine
Alice Zhou: The Johns Hopkins School of Medicine
Kristy Koenig: The Johns Hopkins School of Medicine
Kasinath Kuravi: United Therapeutics Corporation
Farzana Rahman: United Therapeutics Corporation
Lori Sorrells: United Therapeutics Corporation
Lars Burdorf: United Therapeutics Corporation
Kristina DeSmet: United Therapeutics Corporation
Daniel Warren: The Johns Hopkins School of Medicine
Leigh Peterson: United Therapeutics Corporation
Marc Lorber: United Therapeutics Corporation
David Ayares: United Therapeutics Corporation
Andrew Cameron: The Johns Hopkins School of Medicine
Kazuhiko Yamada: The Johns Hopkins School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-7

Abstract: Abstract Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials.

Date: 2024
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DOI: 10.1038/s41467-024-47679-6

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