Washington - Many patients who need kidney transplants may never get them because their bodies are abnormally primed to attack donated organs.
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, who lives in a Washington suburb, 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 is promising work that comes as the country'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 in the United States to get a kidney transplant.
That is crucial, because "your chance of getting successfully transplanted decreases with time," said Dr. Keith Melancon of Georgetown University Hospital in Washington, Preloh's surgeon and a leader in the small but growing field of incompatible kidney transplants.
More than 77,000 people are on the U.S. waiting list to receive kidneys from deceased donors. Yet fewer than 17,000 transplants a year are performed, about 10,500 of them from deceased donors and just over 6,000 from living donors, relatives or friends who offer help to a specific patient. The wait can stretch four to five years, and more than 4,000 patients die on the waiting list each year.
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 is called antibody-mediated rejection, where patients increasingly are "sensitized": their bodies produce antibodies that are supervigilant at attacking most available kidneys. What causes that? Pregnancy, blood transfusions, a previous transplant, increased time on dialysis. So longer transplant wait times are fuelling 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 are treatments pioneered at a few U.S. hospitals and now slowly spreading.
That is not potent enough treatment 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 this 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 tissue.
Melancon, who moved from Johns Hopkins University in Baltimore, Md., to Georgetown in the U.S. capital to spread his 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 last week as she recovered.
