Technique Eliminates Need for Prolonged Immunosuppression in Kidney Transplants

By Gene Emery

June 16, 2022

NEW YORK (Reuters Health) - Doctors at Stanford University School of Medicine in California say they have developed a way to transplant kidneys without the need for long-term immunosuppression.

The technique first requires someone - usually a parent but potentially a sibling or child - to donate stem cells that are transplanted to retrain the patient's immune system. When a kidney from the same donor is transplanted into the patient, the body believes that the donated organ belongs there and rejection does not occur.

The method has been tested in three children and in each case the donor was a parent. Details are published in Thursday's New England Journal of Medicine.

"We now have a safe approach to completely eliminate the use of chronic pharmacological immunosuppression," chief author Dr. Alice Bertaina, chief of the stem-cell-transplant program at Stanford, told Reuters Health by phone.

She said "there is no reason why this is not going to work" in a wide range of cases where a transplant is required for a child or an adult.

"Now that we have proof that this is safe and doable, we can expand these results," she added. "Our goal is to eventually be able to do this in a completely mismatched donor."

But so far it's only been done on the three children, all of whom have a rare genetic condition known as Schimke immuno-osseous dysplasia. It is found in roughly 1 out of every 1 million to 2 million children, producing short stature, a weakened immune system, kidney disease and other problems. Most require a kidney transplant to survive.

In follow-ups ranging from 22 to 34 months, those children have experienced normal renal function without immunosuppression. The treatment also seems to fix defects in the child's immune system.

"Our strategy resulted in rapid and persistent full donor lymphoid and myeloid engraftment and complete discontinuation of all immunosuppression by day 30 after kidney transplantation, without severe GVHD (graft-versus-host disease)," the team writes.

Typically, a transplanted kidney is good for 12 years if it comes from a deceased donor and 19 years if it's donated by a living person.

A key to the technique is depleting the to-be-transplanted blood of alpha-beta T cells and CD19 B cells. In the three children, the kidney transplant was done 5 to 10 months later.

All three initially received immunosuppressive drugs after the surgery, but those were tapered and eliminated by the 30th day.

The children also seem to have more energy and less fatigue, the researchers said.

Transplant recipients who avoid organ rejection face problems associated with the immunosuppressive drugs, including a greater risk of cancer, diabetes and hypertension, that reduce quality of life.

"With this approach," Dr. Bertaina said, "we can avoid that and we can give people back a normal life."

SOURCE: https://bit.ly/3tu6vQh The New England Journal of Medicine, online June 16, 2022.

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