Ingenious Technique Leads To Kids Having Kidney Transplants Without Immune Suppression

Organ transplants can quite literally save lives, but they also come with strings attached – often including a lifetime of immunosuppression drug treatments required to keep the immune system in check, lest it reject the transplanted organ as a foreign invader.

Now scientists are reporting on three successful kidney organ transplants, carried out in children in California, without the need for immune suppression. The transplants used a new method that minimizes the risk of the new kidney getting rejected.

This means freedom from immunosuppressants and the associated side effects, which aren't always pleasant (and include an increased risk of cancers and diabetes). It also reduces the chance of a second transplant being required due to rejection of the first one.

"Safely freeing patients from lifelong immunosuppression after a kidney transplant is possible," says Alice Bertaina, an associate professor of pediatrics at Stanford University in California.

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The innovative technique works by safely transplanting the donor's immune system into the patient – via stem cells from bone marrow – before the kidney also moves over: dual immune/solid organ transplant or DISOT. This has been tried before, but with a limited amount of success.

Here, an extra process was added. The researchers performed an alpha-beta T cell and CD19 B-cell depletion, which meant removing the types of immune cells that cause graft-versus-host disease or GVHD – a potentially lethal complication that has been at risk of developing when similar techniques have been used in the past.

With a reduced threat of GVHD, the process was much safer. The removal of the alpha-beta T cells is relatively 'gentle', making it suitable for medically vulnerable children, and it enables genetically half-matched transplants (from a parent). The removed cells recover naturally in the patient in 60-90 days, building up the immune system again.

Other tweaks were made, including a reduction in the toxicity of the chemotherapy and radiation treatment required before the transplant. Still, some pretty grueling preparation work is required to knock out the immune system of the patient and get the body prepared for receiving a new organ.

The three children given the kidney transplants in this way have an extremely rare genetic disease called Schimke immuno-osseous dysplasia (SIOD), which restricts the body's ability to fight off infection and can lead to kidney failure.

"This remarkable experience underscores the potential of combined or sequential hematopoietic stem-cell transplantation and kidney transplantation to correct disorders of hematopoiesis and immunodeficiency and to induce tolerance of the kidney allograft," write Thomas Spitzer and David Sachs from Massachusetts General Hospital in an accompanying editorial.

"SIOD is a rare disorder that involves immunodeficiency, which undoubtedly contributed to the achievement of successful donor HSCT engraftment."

While SIOD and all of its complications remains something the children have to deal with, they are now all the owners of kidneys that are working as they should be. The transplants have been successful for at least 22 and 34 months, the researchers report.

"These were unique patients in which we had to do the stem cell transplant and a kidney transplant," says Bertaina.

"They are doing everything: they go to school, they go on vacation, they are doing sports. They are having completely normal lives."

The next steps are to expand the number of patients and the number of conditions that this could work for, since for now it's only been demonstrated in patients with SIOD, making them especially suited to the procedure.

Of particular interest to the research team are patients who have already had a kidney transplant rejected by their bodies. That happens in up to half of all cases in children, leading to hypersensitized immune systems that most likely wouldn't accept a second kidney through a normal transplant procedure.

Children will be the first to benefit, then the researchers are going to work up to older ages. Eventually, the technique could even be adapted to cover transplants of organs other than kidneys, but it's going to take a while.

"That's a challenge, but it's not impossible," says Bertaina.

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