Captopril may limit radiation kidney damage in bone marrow transplant patients

Researchers at the Medical College of Wisconsin in Milwaukee have found that the risk of radiation injury in normal tissue after exposure may be reduced by a drug in common use. Their study in press appears in the on line issue of the International Journal of Radiation Oncology, Biology and Physics.

It suggests that long-term administration of the drug captopril, starting at three weeks after patients receive total body irradiation in preparation for bone marrow transplantation (BMT), showed a favorable trend for better long-term kidney function and better long-term patient survival. Chronic kidney failure continues to be a major complication in these patients caused by radiation injury.

“The research holds promise, not only for protection of healthy tissue during radiation therapy, but also because it may lead to strategies for protection from radiation injury after nuclear accidents,” says Eric P. Cohen, M.D., professor of medicine in the division of nephrology, and principal investigator for the study. “Our findings overturned the former dogma that normal tissue radiation injury is untreatable,” he says.

Kidney failure is a well known and serious complication of BMT and occurs in up to 50 percent of patients within the first 30 days after transplantation, increasing early mortality. Chronic kidney failure is also common and affects the health and well being of people otherwise cured of the cancer for which the BMT was performed.

In a double-blind placebo-controlled trial, the team tested captopril on 52 adults and three children undergoing bone marrow transplant from July 1998 to January 2006 at Froedtert Hospital and Children's Hospital of Wisconsin, both major teaching affiliates of the College. When compared to a placebo, captopril-treated subjects had better kidney function and better patient survival.

“The statistics do not show a definite significant value, but the trends are there,” Dr. Cohen says.

Captopril is an angiotensin-converting enzyme (ACE) inhibitor; a class of drugs that help relax blood vessels, and is currently approved by the U.S. Food and Drug Administration for treatment of hypertension, heart failure, and diabetic nephropathy. Because Captopril may cause leukopenia, the study drug was not started until the new marrow had engrafted in the participants. Leukopenia is a condition in which the white blood cells fall below normal.

“The three-week delay in administration of the drug was justified by our animal studies in the late 1990s which showed that a delayed start of captopril could successfully prevent radiation injury to the kidney,” Says Dr. Cohen.

“In an earlier 1992 animal study, published in Radiation Research, we found that captopril was effective in treating chronic kidney damage and its progression after total body irradiation. That showed that normal tissue radiation injury can be treated,” he says.

Dr. Cohen's faculty colleagues on the team include, co-investigator John E. Moulder, Ph.D., professor of radiation oncology; William R. Drobyski, M.D., professor of medicine; Jakob Passweg, M.D., then research associate, now chair of hematology, University of Geneva; and Mark B. Juckett, M.D., associate professor, in the division of neoplastic diseases and related disorders; Amy A. Irving, B.A., research technologist in radiation oncology; John P. Klein, Ph.D., professor of population health and director of biostatistics, and Julie-An M. Talano, M.D., assistant professor of pediatrics.

The study was funded by the National Institutes of Health's National Cancer Institute, and by a grant from the American Cancer Society.