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Selection of Patients for the Initial Clinical Trials of Kidney Xenotransplantation

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Clinical Xenotransplantation

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Abstract

There is a critical and continuing shortage of deceased human donor kidneys for transplantation in patients with end-stage renal disease (ESRD). This could be resolved if kidneys from genetically engineered pigs offered an alternative with an acceptable clinical outcome. Experimental studies suggest that a genetically engineered pig kidney would function for a prolonged period (months or even years) if transplanted into a human recipient. We suggest it would be ethical to offer a pig kidney transplant to selected patients whose life expectancy is less than the time it will take for them to obtain a deceased human donor organ. The median waiting period in the USA for a patient with ESRD to obtain a deceased human donor kidney is 3.9 years, by which time approximately 35% of transplant candidates may have died or been removed from the wait-list. Those of blood group B or O may experience a significantly longer waiting period (>7 years). Many of these patients will not remain alive long enough to receive a deceased human donor organ and therefore may welcome the opportunity of entering the first clinical trial of genetically engineered pig kidney transplantation. The current (limited) evidence is that, even if the patient becomes sensitized to pig antigens, this will not be detrimental to subsequent allotransplantation. In the future, the pigs will also be manipulated to control the adaptive immune response, thus enabling exogenous immunosuppressive therapy to be significantly reduced or, indeed, ultimately unnecessary.

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Abbreviations

ESRD:

End-stage renal disease

HLA:

Human leukocyte antigen

NHPs:

Nonhuman primates

PERVs:

Porcine endogenous retroviruses

SLA:

Swine leukocyte antigen

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Acknowledgment

Work on xenotransplantation at the University of Alabama at Birmingham is supported in part by NIH NIAID U19 grant AI090959 and in part by a grant from United Therapeutics, Silver Spring, MD (the parent company of Revivicor, Blacksburg, VA, that provides UAB with genetically engineered pigs).

Conflict of Interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham (UAB), Birmingham, AL, USA

    David K. C. Cooper, Abhijit Jagdale, Douglas J. Anderson & Devin E. Eckhoff

  2. Division of Nephrology, Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, USA

    Roslynn B. Mannon, Vineeta Kumar & Robert Gaston

  3. Division of Transplantation, Department of Surgery, University of Alabama at Birmingham (UAB), Birmingham, AL, USA

    Michael J. Hanaway

Authors
  1. David K. C. Cooper
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  2. Abhijit Jagdale
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  4. Vineeta Kumar
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  6. Michael J. Hanaway
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  8. Devin E. Eckhoff
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Correspondence to David K. C. Cooper .

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Editors and Affiliations

  1. Xenotransplantation Program, University of Alabama at Birmingham, Birmingham, AL, USA

    David K. C. Cooper

  2. Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA

    Guerard Byrne

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Cooper, D.K.C. et al. (2020). Selection of Patients for the Initial Clinical Trials of Kidney Xenotransplantation. In: Cooper, D.K.C., Byrne, G. (eds) Clinical Xenotransplantation. Springer, Cham. https://doi.org/10.1007/978-3-030-49127-7_14

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  • DOI: https://doi.org/10.1007/978-3-030-49127-7_14

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