Clinical Pig Kidney Xenotransplantation: How Close Are We?
clinical trial
genetically-engineered
kidney
nonhuman primates
patients
pigs
selection
xenotransplantation
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
pubmed:
4
12
2019
medline:
17
7
2020
entrez:
4
12
2019
Statut:
ppublish
Résumé
Patients with ESKD who would benefit from a kidney transplant face a critical and continuing shortage of kidneys from deceased human donors. As a result, such patients wait a median of 3.9 years to receive a donor kidney, by which time approximately 35% of transplant candidates have died while waiting or have been removed from the waiting list. Those of blood group B or O may experience a significantly longer waiting period. This problem could be resolved if kidneys from genetically engineered pigs offered an alternative with an acceptable clinical outcome. Attempts to accomplish this have followed two major paths: deletion of pig xenoantigens, as well as insertion of "protective" human transgenes to counter the human immune response. Pigs with up to nine genetic manipulations are now available. In nonhuman primates, administering novel agents that block the CD40/CD154 costimulation pathway, such as an anti-CD40 mAb, suppresses the adaptive immune response, leading to pig kidney graft survival of many months without features of rejection (experiments were terminated for infectious complications). In the absence of innate and adaptive immune responses, the transplanted pig kidneys have generally displayed excellent function. A clinical trial is anticipated within 2 years. We suggest that it would be ethical to offer a pig kidney transplant to selected patients who have a life expectancy shorter than the time it would take for them to obtain a kidney from a deceased human donor. In the future, the pigs will also be genetically engineered to control the adaptive immune response, thus enabling exogenous immunosuppressive therapy to be significantly reduced or eliminated.
Identifiants
pubmed: 31792154
pii: ASN.2019070651
doi: 10.1681/ASN.2019070651
pmc: PMC6934994
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
12-21Subventions
Organisme : NIAID NIH HHS
ID : U19 AI090959
Pays : United States
Informations de copyright
Copyright © 2020 by the American Society of Nephrology.
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