Stem Cell Therapy Might Help Kidney Transplant Patients

WEDNESDAY Oct. 5, 2011 -- A novel stem cell therapy given shortly after a kidney transplant allows some patients to cast away the medicines meant to keep their body from attacking the new organ, according to a small new study from the Stanford University School of Medicine.

Kidney transplants are common in the United States and while they can greatly improve quality of life for someone with kidney failure, post-transplant life still carries challenges.

A lifelong cocktail of drugs is required to help a transplant patient ward off rejection of the new kidney. The powerful medicines have serious side effects, too, including an increased risk for type 2 diabetes, certain cancers, heart disease, and infection. Though meant as a protective therapy, some immune-suppressing drugs can contribute to damage and the eventual loss of the transplanted kidney.

In a letter in the Oct. 6 New England Journal of Medicine, Dr. Samuel Strober describes the protocol he invented and reports on data from 12 kidney transplant patients who received a new kidney from a "perfect match," typically a sibling. Eight of the patients, who ranged in age from 22 to 68 and underwent the stem cell therapy, have now been off immune-suppressing drugs for at least a year. For some, the drug-free stretch has lasted as long as three years, Strober said.

"Organ transplantation has been a very successful enterprise in treating people with organ failure kidneys, hearts, the lungs. These have been life-saving procedures. But the price people still have to pay is lifelong use of medications that prevent rejection," said Strober, an immunologist and professor of medicine at Stanford.

Strober said his new method, honed over 30 years of research in mice, involves a combination of radiation, donor stem cells, and antibodies (proteins that help deplete some of the patient's own immune cells).

Following transplant surgery in the hospital, the kidney recipient receives radiation targeted at the lymph nodes, spleen and thymus gland to temporarily weaken the immune system. The antibodies are given then, too. Ten days later, the organ donor's stem cells, called hematopoietic progenitor cells -- which form blood and immune-system cells -- are infused into the new kidney patient on an outpatient basis. The donors stem cells, over time, differentiate and join with the transplant patients own immune system, making it more receptive to the donor kidney, Strober said.

A couple of immunosuppressant drugs are given early on, too, he said, but the patient is weaned off of them if no signs of rejection appear within the early months.

"The goal of the study was to try and eliminate the use of lifelong drugs and keep the transplant. So far, so good," Strober said, referring to the eight study patients who no longer take anti-rejection medication and whose kidneys were functioning well.

Strober's letter noted that one patient, who had discontinued anti-rejection drugs for three years, eventually had a heart attack and later died while exercising.

The research holds promise for improving more lives down the road, said Dr. David Scadden, a professor of medicine at Harvard University and co-founder and co-director of the Harvard Stem Cell Institute and the Harvard University Department of Stem Cell and Regenerative Biology.

"I am very excited about this study. The problem of keeping people on chronic immune-suppressing drugs is very significant. To have the opportunity to use stem cells as a way to overcome that is very creative and based on really sound science," said Scadden.

The news is an update on a similar but smaller study the authors published in NEJM several years ago, said Dr. Niraj Desai, director of the Kidney and Pancreas Transplant Program at Johns Hopkins Hospital.

"While the findings were similar, this involved a longer follow-up. One thing you're always concerned about is how long a tolerant state will last," said Desai, who added that the next step would be to test the Stanford approach in patients who are not perfect matches -- for instance, an adult child donating to a parent.

Strober said he and his colleagues are already recruiting such "half-matches," whose immune systems are less compatible, for the next leg of the study funded by a U.S. National Institutes of Health grant.

If such an approach were to be successful long-term in a large number of patients, there would likely be health care cost benefits, too, said Dr. Bryan Becker, past president of the National Kidney Foundation, and assistant vice president for health affairs at the University of Illinois.

The number of kidney transplants has been climbing in recent years. According to the National Kidney Foundation, 16,901 procedures were performed in the United States in 2010, compared with 16,634 in 2007.

Strober said the new treatment tallies as much as $40,000 annually but would pay for itself over time, while immune-suppressing drugs add up to between $10,000 and $15,000 a year.

While a transplant from a living sibling who's a match can last 25 to 30 years on average with current treatments, a kidney from a deceased donor typically lasts only about 12 years, he said.

Organ failure is costly, about $80,000 the year it occurs, said Strober. To eliminate a second transplant would cut medical spending significantly, as would eliminating the need for dialysis, a pricey (about $70,000 annually) and time-consuming blood-cleansing process that kidney failure patients must undergo three times a week.

It's too early to declare the novel post-transplant approach as something that should be an everyday practice, said Scadden, who hopes other medical centers will become involved to help further the research.

"If you just think about what these patients go through, they have had so much to deal with already. They have been on dialysis, then they've waited for a transplant, and then they finally get the chance to resume life and they have to take these medications that have side effects. To be able to get away from that constant reminder and burden has always been a hoped-for outcome and I celebrate the team that got it this far," said Scadden.

Posted: October 2011


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