New kidney-restoring therapy in sight.

The human kidney has the uncommon ability to regenerate damaged tissues. So when acute renal failure strikes - from temporary loss of blood supply, adverse drug reactions, or other causes - physicians maintain their patient's nutrition, fluid levels, and blood pressure and let the body's natural repair systems do the rest. However, supportive therapy is not always successful: Acute renal failure - a common complication of illness and surgery - still contributes to the death of 50,000 people annually.

Now, a study offers compelling evidence that a protein called insulin-like growth factor-I (IGF-I) may eventually provide physicians with the first active therapy for acute renal failure. Such treatment would accelerate the natural healing process, shorten hospital stays, and reduce the death rate in hospitalized patients who develop acute kidney failure.

Nephrologist Steven B. Miller of the Washington University School of Medicine in St. Louis described this research, which will appear in the Dec. 15 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, at last week's meeting of the American Society of Nephrology in Baltimore, Md.

In the study, Miller induced the same type of tissue damage in rats that causes most hospital-acquired renal failure in humans. He then treated the animals with several growth factors - proteins that stimulate cells to divide, enlarge, or differentiate.

Miller observed that IGF-I and one of the other growth factors, epidermal growth factor (EGF), shortened the animals' recovery period. Both proteins also reduced the number of animals that died from their injuries. Only IGF-I alleviated the physical wasting that accompanies renal failure.

This is not the sole, nor the most important, advantage of IGF-I over EGF, Miller says. Previous research has already shown that the drug can be safely administered to humans systemically, for example in the form of a pill or injection. Right now, this does not seem to be true of EGF, which actually decreases kidney function when given to healthy animals or humans, Miller notes. Scientists have also found EGF receptors on certain human tumors. Nobody knows whether such tumors would grow or shrink in the presence of EGF, he says.

Miller expects that positive results from current research; including his own, will continue to increase IGF-I's chances of entering human clinical trials. "IGF-I is far ahead of the game," he says. "We're closer to being able to apply this clinically since it's already been used in people."

Based on the strength of the rat studies and on IGF-I's history of safe use in humans, Miller speculates that clinical tests of the protein for treating acute renal failure could begin soon. He and his colleagues have drawn up an experimental protocol for such a trial and have discussed the possibility with Genetech, Inc., the San Francisco-based bio-technology company that supplied the IGF-I used in the experiments. "We'd like to believe human trials could start within a year," he says, "but I don't know that as a fact."