Three children who have undergone kidney transplants in California will likely be spared having to take anti-rejection drugs, thanks to an innovative technique that eliminates the need for lifelong immunosuppression, according to groundbreaking new research.
Stanford Medicine scientists detailed the cases Wednesday in the New England Journal of Medicine. All three children have an extremely rare genetic condition called Schimke’s immuno-osseous dysplasia, or SIOD, which often destroys a person’s ability to fight infection and leads to kidney failure. In each case, a relative donated stem cells taken from the bone marrow, as well as a kidney.
About three years after transplants, children have normal kidney and immune system function. The technique – called a dual immune/solid organ transplant – 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 to affect only a few dozen children worldwide – experts in the field of kidney transplantation say the results seen in these children are extremely promising for transplants in general.
“There is no organ transplant, be it kidney, liver, pancreas, lung, heart, that doesn’t have the same long-term complications of the highly efficient immune system of the body,” said Dr. Amit Tevar, surgical director of the Kidney and Pancreas Transplant Program at the University of Pittsburgh Medical Center.
Getting the body to not reject 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 view a given organ as a threat worthy of attack.
“It’s groundbreaking,” Tevar, who is not associated with the research, said of the new report.
A breakthrough in kidney transplantation could have a huge impact. Nearly 90,000 people in the United States are waiting for a new kidney, according to the 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 to get a kidney transplant without having to use very strong drugs with side effects,” he said. “It opens up these new approaches.”
Additionally, it could eliminate the need for additional organ transplants in recipients. Donated organs usually only last a decade or two before succumbing to rejection and needing replacement.
But because of the immune tolerance achieved in these cases, “those kidneys are going to last forever,” said study author and Stanford associate professor of pediatrics Dr. Alice Bertaina.
‘Return to Life’
While organ transplants have revolutionized the field of medicine – allowing patients to live much longer than they would otherwise – they come with a serious and life-threatening threat of organ rejection.
Recipients are usually required to continue taking drugs to suppress their immune system for as long as they have the donated organ. These drugs increase the risk of serious problems, such as high blood pressure, cancer, and infections serious enough to require hospitalization.
Even as families with children who have had organ transplants try to resume normal childhood activities, they should still be aware of the risks of disease and infection, said Dr. Eliza Blanchette, pediatric nephrologist at the Children’s Hospital Colorado. “Many of them still live with these worries.”
Patients are also prone to a life-threatening reaction called graft versus host disease, which occurs when newly transplanted cells attack the recipient’s body.
These are risks Jessica and Kyle Davenport of Muscle Shoals, Alabama, were willing to take when they took their two children — both born with SIOD — to Stanford for treatment in 2019.
Kruz, who turns 9 next month, and her 7-year-old sister Paizlee are just the second set of siblings in the world documented with SIOD, said Jessica Davenport. The condition is a type of dwarfism that affects several systems in the body. It is usually characterized by an inability to thrive, kidney failure and a deficiency of T cells, which help the body fight infections.
In 2019, the family traveled to California from their home in Alabama to undergo the lengthy stem cell and kidney transplant process. Jessica Davenport donated her bone marrow and a kidney to her son Kruz, while Kyle Davenport donated her bone marrow and a kidney to her daughter Paizlee.
The foursome stayed in the hospital for a year thanks to bone marrow and kidney donations. The process includes grueling cycles of chemotherapy and radiation therapy for children before organ transplants, as well as the times and risks of surgery for both parents.
“When you’re in there, you have your game face,” Davenport said. “But when we look back, it’s like I can’t believe we actually did this.”
A third child in the report has not been identified. Bertraina said the child, a girl, had been dependent on dialysis in the past, which affected her quality of life.
Almost two years after the operation, “this patient has come back to life,” she said.
Reduce the need for immunosuppressive drugs
Five children with SIOD in other parts of the world have already undergone double immune/solid organ transplantation. But four died, either from graft-versus-host disease or extreme toxicity from the drugs needed to knock out the immune system before the transplant.
The young Stanford patients underwent a relatively similar process of chemotherapy, radiation and other immunosuppressive drugs before the stem cell transplant so their bodies had a better chance of accepting the new cells.
But Stanford doctors modified this diet 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.
There are limits to the procedure. Although children’s kidneys and immune systems are working well at the moment, these transplants are not a cure for SIOD. Kruz and Paizlee continue to have complications, including debilitating migraines and risks of stroke and other cardiovascular issues.
It is not known if the new kidneys will last a lifetime.
“There are many other types of kidney disease where the body still produces factors to damage that kidney,” Rabb said. “Even if you’re not immunocompromised, the original disease may recur.”
Future progress based on these cases will likely depend on whether scientists can see if they can make the method work for patients who have fully functioning T cells, and therefore a more robust immune system to overcome.
Still, the new research “gives us a lot of clues as to how this can be accomplished through future studies in people who have normal T cell systems,” said UPMC’s Tevar.
Bertaina and her team began studying this protocol in 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 immune systems allow Kruz and Paizlee Davenport to experience life in a way that was previously impossible.
“They 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 grow into children.”
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