A new method of kidney transplantation can eliminate the need for immune drugs, says the report.

In California, three children with a kidney transplant will be saved from rejection against rejection thanks to an innovative approach that eliminates the need for lifelong immunosuppression, new research says.

Stanford medical scientists reported the incident in the New England Journal of Medicine on Wednesday. All three children have a rare form of immune-ossified dysplasia, or SIOD, which destroys a person’s ability to fight infection and leads to kidney failure. In each case, the parents donated bone marrow stem cells as well as kidneys.

Three years after the transplant, the children’s kidneys and immune system are functioning normally. A technique called double immune / solid organ transplantation involves stem cell transplantation, which trains the immune system not to refuse subsequent kidney donation. The protocol used at Stanford is not new, but it is a success.

Although SIOD is so rare – it is thought to affect several dozen children around the world – experts in the field of kidney transplantation say the results observed in these children are generally promising for transplantation.

“There is no organ transplantation that is a long-term complication of the body’s highly effective immune system, whether it’s the kidneys, liver, pancreas, lungs, or heart,” the doctor said. Amit Tewar is the surgical director of the Kidney and Pancreas Transplant Program at the University of Pittsburgh Medical Center.

According to Tevar, avoiding rejection of a transplanted organ has always been a difficult struggle. “The Holy Grail of Transplantation is Immune Tolerance,” so the body does not see the donor organ as a threat worthy of attack.

“It’s justified,” Tewar, who is not linked to the study, said of the new report.

Advances in kidney transplantation can have a major impact. About 90,000 people in the United States are waiting for a new kidney, the United Organ Distribution Network.

Dr. Hamid Rabb, medical director of the Johns Hopkins Kidney Transplant Program in Baltimore, called the study “interesting.”

“It would be amazing if there were methods that do not require kidney transplants and the use of very powerful drugs that have side effects,” he said. “It opens up new possibilities.”

In addition, it may eliminate the need for additional organ transplants in recipients. Donor bodies generally live only ten or twelve years before they need to be rejected or replaced.

But because of the immune tolerance achieved in these cases, “these kidneys will last forever,” the doctor said. Alice Berthaine, author of the study and associate professor of pediatrics at Stanford.

‘Back to Life’

Although organ transplants revolutionized the medical field, they allowed patients to live longer than ever before – with the serious and potentially fatal risk of organ rejection.

Recipients are often required to take medication to weaken the immune system until they have a donor organ. These medications increase the risk of serious problems such as high blood pressure and infections that require hospitalization.

Although families with children who have had organ transplants try to return to normal childhood activities, they should always be aware of the risk of disease and infection, the doctor said. Eliza Blanchett, pediatric nephrologist at Colorado Children’s Hospital. “Most of them always live with those worries.”

Patients also experience a potentially fatal reaction called transplant host disease when newly transplanted cells attack the recipient’s body.

Those risks were Jessica and Kyle Davenport of Muscular Shoals, Alabama, who were ready to take their two children, born in 2019 with SIOD, to Stanford for treatment.

Cruz, who turns 9 next month, and her 7-year-old sister, Paisley, are just the second set of siblings in the world to be documented by SIOD, says Jessica Davenport. A condition is a type of dwarfism that affects several systems in the body. This is often due to a lack of growth, kidney failure, and a lack of T cells that help the body fight infections.

Cruz and Paisley Davenport are only the second group of brothers in the world to be documented by the SIOD.family photo

In 2019, the family moved to California from their home in Alabama to undergo a lengthy process of stem cell and kidney transplantation. Jessica Davenport donated her bone marrow and one kidney to her son Cruz, and Kyle Davenport donated his bone marrow and kidney to his daughter Paisley.

Four people received both bone marrow and kidneys as donors and were hospitalized for a year. This process involves complex rounds of chemotherapy and radiation for children before organ transplant surgery, as well as the hours and risks of both parents.

“When you get into it, you have a game,” Davenport said. “But when we look back, I can’t believe we actually did that.”

The report did not identify a third child. According to Bertraina, the boy and girl were previously dependent on dialysis, which affected his quality of life.

Nearly two years after the operation, “this patient was resurrected,” he said.

Reducing the need for immunosuppressive drugs

Five children who had SIOD parts of the world had previously been replaced by another double immune / solid organ transplant. However, four of them died before transplantation or because of the toxicity of the drugs needed to destroy the immune system.

In young patients at Stanford, chemotherapy, radiation, and other immunosuppressive drugs have a relatively similar process before stem cell transplantation, so their bodies are able to accept new cells.

However, Stanford doctors changed the regimen specifically for these vulnerable children to reduce the toxic effects. They also modified the collected stem cells before transplanting them to patients to prevent them from developing anti-host disease.

There are restrictions on the procedure. Although children’s kidneys and immune systems are now functioning well, these transplants are not a cure for SIOD. Both Cruz and Paisley have problems, including migraines and strokes and other cardiovascular problems.

It is unknown whether the new kidneys will last a lifetime.

“There are many other types of kidney disease in which the body still produces factors that damage that kidney,” Rabb said. “Even if you don’t have immunosuppression, the initial disease may recur.”

Future achievements based on these cases may depend on whether scientists know whether T cells can work for fully functioning patients and, therefore, whether they can overcome the immune system.

However, the new study “gives us a lot of hope that this could be achieved through future research in people with a normal T-cell system,” UPMC Tewar said.

Berthaina and her team began studying the protocol in other children with renal insufficiency, including those whose bodies had previously rejected their transplanted kidneys.

According to him, this method can be used to restore the immune systems of people who once received an organ transplant, reducing or eliminating their need for lifelong immunosuppression.

Fully functioning kidneys and immune systems allow Cruz and Paisley Davenport to experience life in ways previously impossible.

“They actually go to birthday parties, Thanksgiving and Christmas with our family,” Davenport said. “It makes me so happy to see them become children.”

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