Nephrology

Desensitization Brings Hope to Children Waiting for a Kidney

Dr. Michael Seifert is a nephrologist at Children’s of Alabama.

A new protocol at Children’s of Alabama is giving sensitized children who need a new kidney a brighter glimmer of hope for successful donor match and transplant.

Children who need a kidney transplant typically wait about a year or two for an organ. But if they’ve been exposed to external blood products, been pregnant or had a previous organ transplant, they could find themselves waiting up to five times longer. That’s because they’ve become sensitized to certain proteins that are foreign to their immune system, which results in high antibody levels that react to foreign tissues. “That makes finding a compatible transplant for them really, really problematic,” pediatric nephrologist Michael E. Seifert, M.D., said. Plus, those antibodies significantly increase the risk of an immediate rejection or graft failure.

Historically, finding a compatible kidney donor for sensitized patients has been challenging, but thanks to a process called desensitization, that’s changing for some. It involves using a combination of immunosuppressive therapies to try to reduce the immune reaction to potential donor organs. Although it’s been used in adults for years, pediatric centers like Children’s have only recently introduced their own protocols. “With these immunomodulatory therapies, we try to turn down the volume on their sensitization,” Seifert said. “You can’t get rid of it altogether. Once a patient is sensitized, they’re always sensitized to some extent.”

The desensitization protocol is a combination of plasmapheresis—a kind of dialysis for blood that removes some of the problematic antibodies and immune proteins—and IV and oral immunosuppressants to prevent the antibodies from returning. Together, Seifert said, “this creates a more potent and widespread ratcheting-down of the immune response that allows some transplants to be done safely.”

The process requires close collaboration between clinicians and the immunology, or HLA, laboratory to choose the right cocktail of immunosuppressants and the right time for transplant. While it’s still challenging to find compatible organs, Seifert says the therapies can help shorten the time on the waitlist for some patients and give them access to more donors.

The team has used the protocol on several children so far, one of whom was able to receive a transplant. “So far, the patients are doing really, really well on it,” Seifert said. “And it’s been a success. But it’s a more challenging transplant because they are still much more likely to reject this kidney than a straightforward kidney transplant. We balance that risk against the risks of remaining on the kidney transplant waitlist for several years, waiting for a compatible donor.”

The children also need more attention post-transplant to keep their immune system at bay without triggering complications like infections, and they’ll have to maintain that throughout their lives, Seifert said. They will also always have a higher risk of rejection and premature graft loss. Yet if the transplant fails, subsequent transplants become more challenging, given greater sensitization.

“It’s a Catch-22,” Seifert said, “in that we achieve our goal, which is getting them a transplant, but it’s a lot more work for us to keep that transplant going.”   

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