Techniques fool highly sensitized immune system into accepting donor kidney

WASHINGTON — Nearly one in three patients who need a kidney transplant may never get one because their bodies are abnormally primed to attack a donated organ. Now doctors are trying new ways to outwit the immune system and save more of those so-called "highly sensitized" patients — often with kidneys donated by living donors, considered the optimal kind. "I feel very lucky. Our son saved my life," said Cynthia Preloh of Arlington, Va., after an unusual combination of blood cleansing and a cancer drug allowed her to receive a kidney from her son that her body otherwise would have destroyed.

It's promising work that comes as the nation's kidney distribution system is beginning a major overhaul. Together, the two efforts aim to make a long-needed dent in the years of waiting it can take to get a kidney transplant.

That's crucial, because "your chance of getting successfully transplanted decreases with time," says Dr. Keith Melancon of Georgetown University Hospital, Preloh's surgeon and a leader in the small but growing field of incompatible kidney transplants.

More than 77,000 people are on the national waiting list to receive a kidney from a deceased donor. Yet fewer than 17,000 transplants a year are performed, about 10,500 of them from deceased donors and a little more than 6,000 from living donors, relatives or friends who offer to help a specific patient. The wait can stretch four to five years, and more than 4,000 patients die on the waiting list each year.

The United Network for Organ Sharing is considering some big changes to the system. There's no formal proposal yet, but there are options under discussion, including wait times defined by kidney function deterioration rather than how early someone gets on the transplant list, and ranking the quality of donated kidneys in a way that would let patients choose one of lesser quality if it means a shorter wait, or try to hold out longer for a better one.

But such changes wouldn't increase available kidneys. Hence the need for the new kidney matchmaking called desensitization aimed at patients like Preloh who otherwise might not get a chance at a new organ.

A transplant starts by matching patient and donor kidney according to blood and tissue type. Today's anti-rejection drugs are so good that tissue-typing can be far from perfect.

A different threat is what's called antibody-mediated rejection, where patients increasingly are "sensitized" — their bodies produce antibodies that are super-vigilant at attacking most available kidneys. What causes that? Pregnancy, blood transfusions, a previous transplant, increased time on dialysis. So longer transplant wait times are fueling sensitization, a vicious cycle.

The more antibodies, the harder it is to find a compatible kidney. So the quest is to rid patients of antibodies targeted to a specific donated kidney, and keep them from making more.

One method: Filtering a patient's blood, called plasma pheresis, before transplant. Another is intravenous immune globulin, or IVIG, a mix of infection-fighting antibodies that basically crowd out the bad kidney kind with run-of-the-mill types. They're treatments pioneered at a few hospitals, including Los Angeles' Cedars-Sinai Medical Center and Baltimore's Johns Hopkins University, and now slowly spreading.

But that's not strong enough for many super-sensitized patients, so a new experiment is testing the lymphoma drug Rituxan, which fights the immune-system cancer by killing certain antibody-producing cells. Cedars-Sinai researchers reported the first preliminary but promising evidence in the New England Journal of Medicine during the summer: Rituxan helped slash antibody levels enough that 16 of 20 patients could be transplanted, and all but one of the new kidneys was working a year later.

Back at Georgetown, Cynthia Preloh, 50, had been told to expect a seven-year wait for a donated kidney when diabetes destroyed her own. Diabetics have particularly poor survival on dialysis and her son offered a faster living donation, but Preloh had too many antibodies that would attack his kidney tissue.

Melancon, who moved from Hopkins to Georgetown to spread this work, hoped Rituxan would give Preloh enough extra desensitization to try the transplant. Her new kidney started working on the operating table, "which was the best thing you could hope to hear," she said as she continued her successful recovery.

Techniques fool highly sensitized immune system into accepting donor kidney 11/24/08 [Last modified: Monday, November 24, 2008 7:35pm]

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