Antifungal Drug May Be New Treatment For Chronic Kidney Disease

April 01, 1997

A common antifungal drug may buy precious time for people with three chronic kidney diseases, delaying their need for dialysis or transplantation, a Johns Hopkins study shows.

The drug, which may promote healing of kidney damage by reducing overproduction of the body's main steroid hormone, could substantially reduce the risk, cost and inconvenience associated with dialysis and transplantation, says Mackenzie Walser, M.D., lead author and a professor of pharmacology, molecular sciences and medicine.

"Our findings are early but promising, and point to a new, long-term approach that may be safe and effective for treating these three types of chronic kidney disease," says Walser, adding that further studies are needed.

Results of the study, supported by the National Institutes of Health and Janssen Pharmaceutica, are published in the April issue of the American Journal of Kidney Diseases.

Researchers studied 20 patients who had one of four types of chronic kidney diseases: glomerular disease, interstitial nephritis, diabetic nephropathy or polycystic disease. The patients were treated with a well-known antifungal drug called ketoconazole for one to four years.

The treatment slowed disease progression by 66 percent in patients with glomerular disease, 55 percent in those with interstitial nephritis and 77 percent in those with diabetic nephropathy. However, the disease rate accelerated by 99 percent in patients with polycystic kidney disease.

In two patients, the treatment continued to slow progression of glomerular disease for four years. Ketoconazole caused some side effects, primarily liver problems, that often occur when it is used to treat fungus infections. Treatment was stopped in three patients because of side effects, and the patients recovered quickly.

Ten years ago, Walser and his Hopkins colleagues found that chronic kidney diseases progressed fastest in patients whose adrenal glands produced a large amount of cortisol, the body's principal steroid hormone, and slowest in patients whose adrenal glands produced little cortisol. They speculated that reducing production of cortisol might slow the progression of kidney failure by promoting the healing of injury to the kidneys. Researchers selected ketoconazole for the study because it has been shown to partially suppress cortisol production. Cortisol belongs to a group of hormones that control the body's use of nutrients and the excretion of salts and water in the urine.

The study's co-author was Sylvia Hill, B.S.


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