TY - JOUR
T1 - Clinical pig kidney xenotransplantation
T2 - How close are we?
AU - Cooper, David K.C.
AU - Hara, Hidetaka
AU - Iwase, Hayato
AU - Yamamoto, Takayuki
AU - Jagdale, Abhijit
AU - Kumar, Vineeta
AU - Mannon, Roslyn Bernstein
AU - Hanaway, Michael J.
AU - Anderson, Douglas J.
AU - Eckhoff, Devin E.
N1 - Funding Information:
Prof. Cooper reports grants from National Institutes of Health National Institute of Allergy and Infectious Diseases during the conduct of the study. Prof. Eckhoff reports grants from United Therapeutics, during the conduct of the study. Prof. Kumar reports receiving honoraria from Mal-linckrodt, outside the submitted work. All remaining authors have nothing to disclose.
Funding Information:
Work on xenotransplantation at the University of Alabama at Birmingham is supported in part by National Institutes of Health National Institute of Allergy and Infectious Diseases U19 grant AI090959, and in part by a grant from United Therapeutics, Silver Spring (the parent company of Revivicor, Blacksburg, VA, that provides University of Alabama at Birmingham with genetically engineered pigs).
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2019070651
DO - 10.1681/ASN.2019070651
M3 - Review article
C2 - 31792154
AN - SCOPUS:85077180463
VL - 31
SP - 12
EP - 21
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
SN - 1046-6673
IS - 1
ER -