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Stanford Report, May 1, 2002

Kidney transplant rejection prevented without drugs


Researchers at the medical center have discovered a way to transplant kidneys without having the patient remain on a lifelong course of immune-suppressing drugs in order to prevent rejection. As an added bonus, the donor kidneys don't even need to come from a relative -- a fact that has limited kidney availability to sick people in need.

"Transplantation is a life-saving procedure, but the price is the lifelong use of immune-suppressing drugs," said Samuel Strober, MD, professor of immunology and rheumatology at the School of Medicine and leader of the study. Strober noted that these drugs leave kidney recipients open to infection and increase future risk of heart disease or cancer.

Results from four patients in the study were presented Sunday in Washington, DC, at the American Transplant Congress by Maria Millan, MD, transplant surgeon at Stanford Hospital & Clinics and assistant professor of surgery. The work will also appear in the journal Transplantation May 15.

Organ rejection after transplantation occurs because the immune system scans for foreign cells. If the immune system in the transplant recipient weren't heavily suppressed, it would attack cells in the transplanted organ, leading to rejection.

Strober said the study asks two questions: can you get patients off the drugs and, if so, for how long? "We feel we can answer yes to the first question," Strober said, adding that so far, two of the four patients in the study are completely free of drugs, with another still tapering off.

This new transplant approach began in the usual way, with surgery followed by immune-suppressing drugs, which were needed to prevent organ rejection while the team completed the next step.

After the transplant, the kidney recipient received small doses of radiation targeted to the immune system along with a drug to reduce the number of cells capable of an immune attack. The team then injected blood stem cells from the kidney donor into the recipient. The stem cells made their way to the recipient's bone marrow where they produced new blood and immune cells that mixed with those of the recipient. After this procedure, the recipient's immune cells recognize the donor's organ as friend rather than foe.

The Stanford team monitored the recipient's new hybrid immune system looking for a mixture of cells from both recipient and donor. These cells were tested and did not attack cells from the donor. This told the team that the new hybrid immune system would not mount an attack against the transplanted organ. The team then weaned the patient away from the immune-suppressive drugs.

Millan said this study represents the direction transplantation will move in the future. In the past, the goal was to have a transplanted organ function in the recipient. Doctors now routinely achieve that goal, and are looking for ways to increase the long-term survival of the transplanted organ while maintaining the recipient's quality of life. "We've topped out on what we can do with drugs," Millan said.

Also on the team were Richard Hoppe, MD, the Henry S. Kaplan-Harry Lebeson professor of radiation oncology; John Scandling, MD, professor of medicine (nephrology); Oscar Salvatierra, MD, professor of surgery and pediatrics; and Judith Shizuru, MD, PhD, assistant professor of medicine (bone marrow transplantation).

Bench-to-bedside approach proving successful in pediatric transplantation research (10/18/00)