Mar. 27, 1998 By Paul E. Ramey
GAINESVILLE, Fla.---Aided by a new $1 million grant from the National Institutes of Health, researchers at the University of Florida are evaluating the feasibility of using a pill to prevent common calcium oxalate kidney stones.
The grant will enable UF College of Medicine pathologist Ammon Peck and colleagues to determine whether kidney stones can be prevented in laboratory rats by giving them a coated pill to replenish a beneficial bacteria called Oxalobacter formigenes. An absence of this intestinal bacteria has been linked to the development of calcium oxalate kidney stones.
Kidney stones affect 5 to 10 percent of the world population, and nearly 1 million Americans suffer from painful kidney stone episodes each year. Nearly $2 billion is spent nationwide every year to treat kidney stones, including surgically removing them or repeatedly aiming high-energy shock waves at them until they disintegrate. The disease is especially prevalent among 30- to 39-year-old men.
Peck's co-investigators include oxalate expert Saeed Khan, a professor of pathology at the UF College of Medicine, and Milton Allison, a professor of microbiology, immunology and preventive medicine at Iowa State University. Harmeet Sidhu, a former UF visiting professor, will serve as a consultant for the study.
Allison first identified O. formigenes as an organism essential to the body's ability to break down harmful oxalate, also called oxalic acid, before it binds with calcium to form crystals that turn into kidney stones. Oxalate is an abundant chemical that forms as a byproduct of digestion. It also is present in many common foods, including tea, broccoli, spinach and chocolate. Excess amounts of this naturally occurring organic compound have been linked to certain heart problems, kidney failure and, in some cases, death.
Results of the UF research also are expected to have applications for other diseases related to an overabundance of oxalate in the body, including cystic fibrosis.
The focus of Peck's study is two-part. "We want to confirm whether the loss of Oxalobacter formigenes leads to a higher risk for producing oxalate," he said. "We also want to determine why the bacteria rarely recolonizes, or regrows, in animals that have become decolonized."
One reason could be that animals and people develop a natural resistance to the organism after it disappears from the body. Some people's intestines also may not provide the proper environment for the bacteria to grow, Peck said.
Why some people lack the vital intestinal bacteria is not known, but overuse of antibiotics has been linked to destruction of the organism.
Peck's identification of two oxalate-degrading genes in 1994 led the way for the development of a new diagnostic test for the bacteria by Ixion Biotechnology Inc., a licensee of the Peck technology. The test will be used in the new federally funded study. In the study, researchers will attempt to reintroduce the bacteria into rats with a coated pill that passes through the stomach and releases in the intestine. The efforts will include variations in dosage, time of delivery and diet, if needed.
Another recent UF study has shown that daily enzyme treatment also may prevent kidney stone formation. Peck and colleagues have found that giving laboratory animals a pill containing an enzyme before and after meals successfully reduces oxalate levels.
It is possible this enzyme treatment could one day be used to manage kidney stones, though Peck said researchers hope to go one step further.
"Most people say, 'Why would you want to use a pill (the enzyme treatment) when you could just put the bacteria back in the gut?' But that's just it. We don't seem to be able to put the bacteria back in and we hope to find out why with the new study."
The new study is supported in part by Ixion Biotechnology, located in the Sid Martin Biotechnology Development Institute at UF's Progress Center in Alachua, Florida. Peck is a co-founder of Ixion, formed in 1993 to develop, manufacture and market products to detect, diagnose, treat and prevent diabetes and kidney stones as well as other related diseases.
Sidhu is Ixion's director of research, oxalate division, and Kahn and Allison are both members of the company's scientific advisory board.
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