Thursday, November 09, 2006

Drug Reduces Kidney-Transplant Rejection Rates

(HealthDay News) -- Most kidney transplant patients have to undergo what's known as "induction therapy" to suppress their immune systems and lessen the chance of the new organ being rejected.

A new study found that one drug, rabbit antithymocyte globulin (brand name Thymoglobulin) was better at reducing the risk of acute rejection than a commonly used medication known as basiliximab -- 15.6 percent of the thymoglobulin group experienced acute rejection compared with 25.5 percent of the basiliximab group.

"Both acute rejections and the severity of the acute rejection rates were much lower," said the study's lead author, Dr. Daniel Brennan, director of transplant nephrology at Barnes-Jewish Hospital and a professor of medicine at the Washington University School of Medicine, in St. Louis.

"It might not sound like a big difference, but it's really quite important. An ounce of prevention is worth a pound of cure. The more severe rejection is, the more treatment is required, and the worse a transplant usually does in the long run," he explained.

Results of the study, which was sponsored by the maker of thymoglobulin, Genzyme, are published in the Nov. 9 issue of the New England Journal of Medicine.

Induction therapy begins on the day a person receives their kidney transplant and continues for several days after. The goal of induction therapy is to suppress the immune system so it doesn't recognize the new organ as foreign tissue. Rejection occurs if the transplant patient's immune system realizes there is foreign tissue present and begins to attack it.

However, a delicate balance has to be maintained, because if physicians suppress the immune system too much, serious infections can occur.

For the new study, 278 high-risk kidney transplant patients were randomly assigned to receive either thymoglobulin (141 patients) or basiliximab (137) for their induction therapy. Those given thymoglobulin received 1.5 milligrams per kilogram of body weight daily, while those on basiliximab were given 20 milligrams daily. Both groups received treatment beginning on the day of transplant through day 4 after transplant. They also were given other immune-suppressing medications.

According to the study, "the design, data collection and analysis were performed by a sponsor, Genzyme," and the data were then reviewed and verified by the study's authors.
The study follow-up lasted 12 months.

During that time, 15.6 percent of the thymoglobulin group and 25.5 percent of the basiliximab group experienced acute rejection. In some cases, rejection was severe enough to require additional treatment with thymoglobulin, for either group. But the incidence of severe rejection was lower in the group that initially received thymoglobulin -- 1.4 percent versus 8 percent in the basiliximab group.

There were no significant differences in the incidence of delayed graft function -- that's the time it takes for the new kidney to start working properly -- or in graft loss or death, according to the study.

There was a greater risk of infection in the thymoglobulin group -- 85.8 percent compared to 75.2 percent for those on basiliximab. But there was a much lower rate of the serious infection cytomegalovirus for those on thymoglobulin -- 7.8 percent versus 17.5 percent for people taking basiliximab.

"This study shows that for those at higher risk, thymoglobulin is clearly the way to go," said Brennan.

Dr. Michelle Josephson is medical director of kidney transplantation at the University of Chicago, and the author of an accompanying editorial in the same issue of the journal. She said, "I think it was great that the authors did a prospective randomized trial, but one of the downsides is that it may not reflect current management."

"Most studies, including this one, use cyclosporine-based immunosuppression, but tacrolimus is more commonly used by most centers today. Also, a lot of centers are using prednisone-free immunosuppression, and prednisone was used in this study. So, I'm not sure how uniformly applicable these results are given current immunosuppression trends," she explained.

However, Josephson added that anything that can be done to reduce the risk of rejection is helpful.

"To the extent that you have less of a risk of a bad rejection, even without an impact on graft survival at one year, [thymoglobulin is] useful. For the patient and their life, it's quite an inconvenience to have rejection. They want to get back to their lives with as few complications as possible," she said.

More information
To learn more about the kidney transplantation process, visit the National Kidney Foundation.

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