• Kidney stone. A team from the University of Houston led by Jeffrey Rimer has discovered a new molecule with the potential to be a more effective inhibitor of kidney stone formation.

Kidney stone. A team from the University of Houston led by Jeffrey Rimer has discovered a new molecule with the potential to be a more effective inhibitor of kidney stone formation. (Photo : University of Houston)

A study has found evidence a compound called "hydroxycitrate (HCA)," which is available as a natural fruit extract, is capable of dissolving calcium oxalate crystals, the most common component of human kidney stones.

This finding could lead to the first advance in the treatment of calcium oxalate stones in 30 years.

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The study the first evidence hydroxycitrate is an effective inhibitor of calcium oxalate crystal growth. It found that under certain conditions, hydroxycitrate is actually able to dissolve these crystals. Researchers also explain how it works.

The findings are the result of a combination of experimental studies, computational studies and human studies, said Jeffrey Rimer, associate professor of chemical engineering at the University of Houston.

Rimer was lead author of the study published Aug. 8 in the online edition of Nature.

Kidney stones are small, hard mineral deposits that form inside the kidneys. They affect up to 12 percent of men and seven percent of women in the United States. High blood pressure, diabetes and obesity can increase the risk of kidney stones whose incidence is rising.

Preventive treatment for kidney stones hasn't changed much over the last three decades. Doctors tell patients who are at risk of developing stones to drink lots of water and avoid foods rich in oxalate, such as rhubarb, okra, spinach and almonds.

They often recommend taking citrate (CA) in the form of potassium citrate, which is a supplement that can slow crystal growth. Some people are unable to tolerate the side effects, however.

The project grew out of preliminary work done by collaborator John Asplin, a nephrologist at Litholink Corporation, who suggested HCA as a possible treatment. HCA is chemically similar to CA and is also available as a dietary supplement.

"HCA shows promise as a potential therapy to prevent kidney stones," the researchers wrote. "HCA may be preferred as a therapy over CA (potassium citrate)."

The head-to-head studies of CA and HCA determined that while both compounds inhibit the growth of calcium oxalate crystals, HCA was more potent and displayed unique qualities advantageous for the development of new therapies.

The team of researchers then used atomic force microscopy, or AFM, to study interactions between the crystals, CA and HCA under realistic growth conditions. The technique allowed researchers to record crystal growth in real time with near-molecular resolution.

Chung noted the AFM images recorded the crystal actually shrinking when exposed to specific concentrations of HCA.

Rimer suspected the initial finding was an abnormality, as it is rare to see a crystal actually dissolve in highly supersaturated growth solutions. The most effective inhibitors reported in the literature simply stop the crystal from growing. It turned out Chung's initial finding was correct.

Once they confirmed it's possible to dissolve crystals in supersaturated solutions, researchers then looked at reasons to explain why that happened.

HCA was also tested in human subjects and seven people took the supplement for three days. This allowed researchers to determine HCA is excreted through urine, a requirement for the supplement to work as a treatment.

While Rimer said the research established the groundwork to design an effective drug, questions still remain. Long-term safety, dosage and additional human trials are needed, he said.

"But our initial findings are very promising," he said. "If it works in vivo, similar to our trials in the laboratory, HCA has the potential to reduce the incidence rate of people with chronic kidney stone disease."

In addition to Rimer and Asplin, authors on the paper include Giannis Mpourmpakis and his graduate student, Michael G. Taylor, of the University of Pittsburgh; Ignacio Granja of Litholink Corporation, and Jihae Chung, a UH graduate student working in Rimer's lab.