UF Researcher Explores Protein’s Role In Kidney Stones

February 20, 1997

GAINESVILLE—The ultimate therapy for people with kidney stones may lie not only in careful meal planning and drinking plenty of water, but also in changing what the body’s cells make, a University of Florida researcher says.

“Everyone forms crystals made of calcium phosphate and calcium oxalate,” said Saeed R. Khan, a professor and basic scientist in the department of pathology at UF’s College of Medicine. “But only some of us develop stones from these crystals. The difference is, some people make proteins that encourage stone development. We need to find a way to force cells to make the `right’ kind of protein to prevent stones from forming.”

Americans spend $2.4 billion annually on treating kidney stones, which can cause recurring bouts of excruciating pain and kidney damage as they block and/or pass through urinary channels. Some stones must be removed surgically, or broken up through shock wave lithotripsy. An estimated 10 percent of the U.S. population will have the urinary tract disorder sometime in their lives, and the incidence is rising.

In the January issue of the Journal of Urology, Khan disputes some long-held assumptions about how kidney stones form. Over time, Khan’s work could lead to changes in medical strategies.

Most stones are composed of a mass of calcium phosphate and calcium oxalate crystals which build up inside the kidneys. The prevailing theory has been that the calcium phosphate crystals form first; they in turn promote the creation of calcium oxalate crystals surrounding them.

Khan developed an alternative view after looking at high-resolution microscopic images of human and rat stones. He noticed that a coating of protein and other organic material lies between the calcium phosphate and calcium oxalate in the stones.

“There is so much protein in there–effectively acting as a barrier between the two types of crystals–that there is no possibility of the phosphate having a direct effect on the crystallization of the oxalate,” Khan said.

“In normal human urine, these proteins keep the crystals away from each other. But in stone-formers, the crystals lose the capacity to stay away from each other. The aggregated crystals become the beginning of a kidney stone.”

People who have one kidney stone run a high risk of forming more. That’s why physicians advise them to take preventive measures to avoid kidney damage. They may be asked to cut down on foods containing oxalate, which can be found in spinach, broccoli and asparagus, for example, and reduce calcium intake.

They also are told to drink enough water to produce more than 2 liters of urine every day because the greater the volume, the lower the concentration of stone-forming substances.

“The idea has been that you should try to stop the formation of calcium phosphate through dietary controls so that the second step, the creation of calcium oxalate, will not happen,” Khan said. “But if it is the protein that is important, the approach will be different. You will start trying to find out why those cells make the proteins that they do. If we know there is a molecular deformity, theoretically we can work to change it.”

The dietary strategy emphasizes the interaction of inorganic calcium compounds, Khan said.

“Research like ours is emphasizing the importance of biological controls of crystallization and stone formation. As we understand more and more, we will be able to develop new protocols to manage stone disease.”