In a ray of hope for thousands of kidney transplant patients, surgeons at New York University Langone Transplant Institute have transplanted a genetically engineered pig kidney that continues to function well after 32 days in a man declared dead by neurologic criteria and maintained with a beating heart on ventilator support.
This represents the longest period that
a gene-edited pig kidney has functioned in a human, and the latest step toward
the advent of an alternate, sustainable supply of organs for transplant.
The procedure, performed on July 14, and
led by Robert Montgomery, chair of the Department of Surgery, and director of the
NYU Langone Transplant Institute, was the fifth xenotransplant performed at NYU
Langone.
Observation is ongoing, and the study
will continue through mid-September 2023, the university said in a statement.
"This work demonstrates a pig
kidney - with only one genetic modification and without experimental
medications or devices - can replace the function of a human kidney for at
least 32 days without being rejected," said Dr Montgomery.
He had previously performed the world's
first genetically modified pig kidney transplant into a human decedent on
September 25, 2021, followed by a second similar procedure on November 22,
2021.
Surgeons with the Transplant Institute
performed two genetically engineered pig heart transplants in summer 2022.
The first hurdle to overcome in
xenotransplants is preventing so-called hyperacute rejection, which typically
occurs just minutes after an animal organ is connected to the human circulatory
system.
By "knocking out" the gene
that encodes the biomolecule known as alpha-gal -- which has been identified as
responsible for a rapid antibody-mediated rejection of pig organs by humans --
immediate rejection has been avoided in all five xenotransplants at NYU
Langone.
To ensure the body's kidney function was
sustained solely by the pig kidney, both of the transplant recipient's native
kidneys were surgically removed.
One pig kidney was then transplanted and
started producing urine immediately without any signs of hyperacute rejection,
said the university.
During the observation phase, intensive
care clinical staff maintained the decedent on support while the pig kidney's
performance was monitored and sampled with weekly biopsies.
Levels of creatinine, a bodily waste
product found in the blood and an indicator of kidney function, were in the
optimal range during the length of the study, and there was no evidence on
biopsy of rejection.
While previous genetically engineered
pig organ transplants have incorporated up to 10 genetic modifications, this
latest study shows that a single-gene knockout pig kidney can still perform
optimally for at least 32 days without rejection.
“We've now gathered more evidence to
show that, at least in kidneys, just eliminating the gene that triggers a
hyperacute rejection may be enough along with clinically approved
immunosuppressive drugs to successfully manage the transplant in a human for
optimal performance -- potentially in the long-term,” said Dr Montgomery.
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