News Release

Making kidney transplants last longer: Large UM study finds newer drug is better

Peer-Reviewed Publication

Michigan Medicine - University of Michigan

Kidney transplant recipients may be able to keep their new organs longer using a drug that was originally designed to prevent only short-term rejection, a new study from the University of Michigan concludes.

A compound called mycophenolate mofetil, or MMF, was found to reduce the risk of losing the new kidney due to chronic, or long-term, kidney failure better than the conventionally used drug azathioprine (AZA). The effect was not just due to MMF's ability to reduce acute rejection responses. In fact, the new results show the relative risk of chronic kidney failure is 27 percent lower with MMF. Both MMF and AZA are used in conjunction with two other compounds as a "triple therapy" to help suppress the body's immune response to a transplanted organ.

The report, based on one of the largest-ever examinations of chronic transplant failure, is being presented May 15 at a joint meeting of the American Society of Transplantation and the American Society of Transplant Surgeons by Bruce Kaplan, M.D., an associate professor of nephrology and co-medical director of renal transplantation in the University of Michigan Health System.

"For those who have endured the pain of kidney failure, the suspense of waiting for a transplant, the ordeal of surgery, and the hurdle of avoiding acute rejection, the threat of chronic rejection and loss of the kidney within a few years still looms," says Kaplan. "Our results suggest that therapy that includes MMF may offer longer kidney and patient survival than AZA by reducing the risk of both acute and chronic failure."

The results, based on data from 66,774 patients who received a new kidney between 1988 and 1997 and whose kidneys survived the first six months after transplant, confirms an effect suggested by much smaller studies at other centers.

For the new report, Kaplan and his colleagues examined the four-year survival of both the kidneys and the patients, as recorded by the U.S. Scientific Renal Transplant Registry. About 8,000 patients in the study population were treated with MMF, either in clinical trials of the drug or after its approval in 1995 to prevent acute rejection.

The study shows that MMF protects against kidney loss due to chronic failure even when the effects of acute failure prevention were eliminated. Nearly 86 percent of the MMF-treated kidneys survived four years, compared to 82 percent of kidneys treated with AZA.

Patients can survive on dialysis even if their new kidneys fail, which on average occurs nine years after transplant. Kidney losses for other reasons besides chronic failure were eliminated from the analysis.

MMF has already shown a great advantage over AZA in guarding against acute kidney failure in transplant patients when taken as part of triple therapy in conjunction with corticosteroids and cyclosporine. It is already a standard part of anti-rejection therapy for adult and pediatric patients who receive a kidney at the UM. In 1998, UM doctors transplanted 198 kidneys.

MMF targets two kinds of white blood cells, called T and B lymphocytes, that the body produces to attack invaders. MMF specifically prevents both kinds of lymphocytes from reproducing in large enough numbers to mount an offense against the transplanted kidney. AZA targets all white blood cells and platelets. Both drugs cause side effects, including nausea, vomiting, diarrhea and low white blood cell counts.

Chronic kidney failure, leading to loss of the transplanted kidney, often occurs because enough lymphocytes are still available to attack the transplanted organ and because of other immune reactions caused by the mismatch of the recipient's antibodies to proteins on the surface of the new kidney's cells.

Protecting against chronic organ failure is important to the individual patient, and to the entire population of transplant candidates. There aren't nearly enough organs -- either from living or cadaveric donors -- to meet the current demand.

Nearly 45,000 Americans are now waiting for a kidney transplant, but only 12,517 kidney transplants were performed in all of 1999. More than 2,300 people died in 1999 while waiting for a kidney transplant.

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MMF is made by Hoffman-LaRoche, Inc. under the name CellCept. AZA is marketed as Imuran.


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