Kidney Deterioration Could Become a Factor in the Choice of Patient for Transplant in US

by Gopalan on Oct 15 2008 2:56 PM

Kidney deterioration could become a factor in the choice of a patient for transplant in the US and not the time when he or she entered the waiting list. Also to be weighed is how long one would survive after the transplant.

Plagued with the ever growing list of patients needing kidney transplant while there is a continuing shortage of organs available for transplant, authorities are considering some key changes in transplant administration.

Experts say it would be a while before the measures contemplated begin to show any result,

and hence indeed organ donation has to be promoted far more aggressively than has been the case so far.

More than 77,000 people are on the national waiting list to receive a kidney from a deceased donor in the US. 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 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, news agency AP reports. There's no formal proposal yet, but there are options under discussion:

Wait times might be defined by kidney function deterioration rather than how early someone gets on the transplant list, to level the field for patients who don't see a specialist right away.

In addition to wait time, matches may weigh recipient and kidney age and medical conditions to maximize what's "life years from transplant." One kidney might last longer in an older person without diabetes than in a younger diabetic, explains Dr. Kenneth Andreoni of Ohio State Medical Center and vice chair of the UNOS kidney committee.

"It's trying to get the balance between having a person live longer because they have the transplant over dialysis, and also looking at how many years in total they would live," he says.

_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.

Such changes wouldn't increase available kidneys. Hence the need for the new kidney match-making called desensitization.

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, Virginia, 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.

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 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 Hopkins to Georgetown in the nation's capital 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 last week as she recovered.

Overhauling the transplant process and choosing the right candidate is 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.

Dr.Sunil Shroff, promoting organ donation in India for long, notes that getting a transplant in the United States when on the waiting list is like winning a lottery.

“The current improvement in diagnosis and treatment of patient's with kidney disease, means more and more are now getting on the waiting list. The demand has far outstripped the supply. This is mainly at present the problem with kidneys and not so much with heart and liver.

“I feel that there is still scope for increasing the deceased donation rate in the United States.”

He also pointed out that the increase in the incidence of diabetes and hypertension had added to the burden of the kidney disease.

“To tackle the problem of shortage, we need to also look at ways of preventing kidney disease which, in turn, could mean more money spent on screening. But the resources have to be mobilized, there is no escape,” Dr.Shroff stressed.