New Kidney Transplant Approach Could Eliminate Need for Immune Drugs, Says Report
Three children who underwent kidney transplants in California will likely be spared ever needing anti-rejection drugs because of an innovative technique that eliminates the need for lifelong immunosuppression, groundbreaking new research suggests.
Stanford Medicine scientists detailed the cases on Wednesday New England Journal of Medicine. All three children have an extremely rare genetic disease called Immunosseous dysplasia according to Schimkeor SIOD, which often destroys a person’s ability to fight off infection and leads to kidney failure. In each case, one parent donated stem cells taken from bone marrow and a kidney.
About three years after the transplant, the children have normal kidney and immune system function. The technique, called dual immune/solid organ transplantation, involves a stem cell transplant that trains the immune system not to reject a subsequent kidney donation. The protocol used at Stanford is not new, but its success is.
Although SIOD is so rare – it is estimated that only a few dozen children are affected worldwide – kidney transplant experts say that the results seen in these children for transplants in general are extremely promising.
“There is no organ transplant, whether kidney, liver, pancreas, lung, heart, that doesn’t have the same long-term complications from the body’s very effective immune system,” said Dr. Amit Tevar, surgical director of the kidney and pancreas transplant program at the University of Pittsburgh Medical Center.
Keeping the body from rejecting a transplanted organ has always been an uphill battle, Tevar said. “The Holy Grail of transplantation is immune tolerance,” meaning that the body does not see a donated organ as an vulnerable threat.
“This is groundbreaking,” said Tevar, who is not associated with the research, of the new report.
Advances in kidney transplantation could have far-reaching implications. According to this, almost 90,000 people in the USA are waiting for a new kidney United Network for Organ Sharing.
dr Hamid Rabb, medical director of the Johns Hopkins Kidney Transplant Program in Baltimore, called the research “exciting”.
“It would be amazing if there were techniques where you could get a kidney transplant and not have to use very strong drugs with side effects,” he said. “That opens up these new approaches.”
In addition, it could eliminate the need for additional organ transplants in recipients. Donated organs generally only last a decade or two before they succumb to rejection and need to be replaced.
But because of the immune tolerance achieved in these cases, “these kidneys are going to last forever,” said Dr. Alice Bertaina, study author and associate professor of pediatrics at Stanford.
‘Back to life’
While organ transplants have revolutionized the field of medicine, allowing patients to live much longer than they otherwise would, they come with a serious and potentially fatal risk of organ rejection.
Recipients generally need to take medication to suppress their immune systems for as long as they have the donated organ. These drugs increase the risk of serious problems like high blood pressure, cancer, and infections serious enough to require hospitalization.
Even as families with children who have had an organ transplant try to return to normal childhood activities, they must always be aware of the risks of illness and infection, said Dr. Eliza Blanchette, pediatric nephrologist at Children’s Hospital Colorado. “Many of them always live with these worries.”
Patients are also exposed to a potentially fatal reaction called graft-versus-host disease, in which newly transplanted cells attack the recipient’s body.
These were risks Jessica and Kyle Davenport of Muscle Shoals, Alabama, were willing to take when they brought their two children — both born with SIOD — to Stanford for treatment in 2019.
Kruz, who turns 9 next month, and his 7-year-old sister Paizlee are only the second group of siblings in the world to be documented with SIOD, Jessica Davenport said. The condition is a type of dwarfism that affects multiple systems in the body. It is generally characterized by an inability to grow normally, kidney failure, and a lack of T cells, which help the body fight off infection.
In 2019, the family traveled to California from their home in Alabama to undergo the long process of stem cell and kidney transplants. Jessica Davenport donated her bone marrow and a kidney to son Kruz while Kyle Davenport donated his bone marrow and a kidney to daughter Paizlee.
The foursome spent a year in the hospital on both bone marrow and kidney donations. The process includes grueling rounds of chemotherapy and radiation for the children prior to organ transplants, as well as the hours and risks of surgery for both parents.
“If you’re in it, keep your game face up,” Davenport said. “But looking back, I can’t believe we actually did that.”
A third child in the report has not been identified. Bertraina said the child, a girl, had previously been dependent on dialysis, which affected her quality of life.
Almost two years after surgery, “this patient has come back to life,” she said.
Reducing the need for immunosuppressive drugs
Five children with SIOD elsewhere in the world have previously undergone dual immune/solid organ transplantation. But four died, either from graft-versus-host disease or from the extreme toxicity of the drugs needed to shut down the immune system prior to transplantation.
The young patients at Stanford underwent a relatively similar process of chemotherapy, radiation, and other immunosuppressive drugs prior to stem cell transplants to give their bodies a better chance of accepting the new cells.
But the Stanford doctors have optimized this regimen specifically for these vulnerable children, reducing the toxic effects. They also modified the harvested stem cells to rid them of the ability to cause graft-versus-host disease before infusing them into patients.
Tcnges worked. at the time of this report, 34, 23 and 22 months had elapsed since transplantation; Kidney function returned to normal with no clinical signs of rejection, the study authors wrote
The procedure is subject to restrictions. Although the children’s kidneys and immune systems are working right now, these implants are not a cure for SIOD. Both Kruz and Paizlee continue to have complications, including debilitating migraines and stroke and other cardiovascular issues.
Whether the new kidneys will last a lifetime is uncertain.
“There are many other types of kidney disease where the body is still producing factors that damage the kidney,” Rabb said. “Even if you don’t have immunosuppression, the oral disease could come back.”
Future advances based on these cases will likely depend on the scientists’ ability to see if they can get the method to work in patients with fully functioning T cells, and therefore a more robust immune system are studying a variety of other children with kidney failure, including those whose bodies had previously rejected their transplanted kidneys.
It’s also possible, she said, that the approach could one day be used to reset the immune systems of people who have already received an organ transplant, reducing or eliminating their need for lifelong immunosuppressive drugs.
Fully functioning kidneys and a fully functioning immune system allow Kruz and Paizlee Davenport to experience life in ways previously impossible.
“You can actually go to birthday parties, Thanksgiving and Christmas with our family,” Davenport said. “It brings so much joy to my heart to see them actually becoming children.”Book. hnksgiving and Christmas with our family,” Davenport said. “It brings so much joy to my heart to see them actually becoming children.”