Calgranulin

Trace amounts of little known protein prevent formation of kidney stones

August 1, 1998

Researchers at the University of Chicago discovered that an anti-inflammatory protein called calgranulin, previously detected only in white blood cells, may play a key role in the prevention of kidney stones.

Sokalingum Pillay, PhD, research associate and assistant professor of medicine at the University, found that calgranulin is present in the kidney and human urine and can--even in minute amounts--stop the growth of calcium oxalate crystals, which is the major component of kidney stones.

His findings will be published in the August 1998 issue of the American Journal of Physiology Renal with co-authors Fredric Coe, MD, section chief of nephrology, and John Asplin, MD, assistant professor of medicine.

"Measuring calgranulin in urine could become a new diagnostic tool for determining if a patient is at high risk for forming kidney stones, and preventive measures could be taken," says Pillay.

He found that calgranulin, which is made up of two distinct subunits, is often defective in stone-formers. "In many people with kidney stones, the subunits don't come together to form the bigger, active protein calgranulin. We suspect this is a factor in their tendency to form stones," says Pillay.

According to the basic laws of chemistry, our kidneys should be chock-full of kidney stones. Although the kidney is supersaturated with calcium and oxalate, the basic components of kidney stones, only three to five percent of people in the Western Hemisphere form them. Most people pass microscopic calcium oxalate crystals with their urine before they can grow into dangerous masses. "It is the natural fate of supersaturated solutions to grow crystals," says Dr. Asplin. "Something must be working to prevent this in the kidneys."

Over the past 10 years, several proteins were found that have some effect on slowing or stopping crystal formation--but none with the potency of calgranulin, which "is more than 20 times more potent than any other known crystal inhibitors," says Pillay.

"Calgranulin exists in trace amounts," says Dr. Coe. "It's effective at preventing crystal formation at concentrations 1 million times lower than the urine concentration of calcium and 100,000 times lower that the urine concentration of oxalate," he says.

When Pillay and Dr. Asplin created artificial solutions that mimic the conditions inside the kidney--minus any crystal-prohibiting proteins--calcium oxalate crystals began to aggregate immediately. When they added minute amounts of purified calgranulin, crystal growth slowed down considerably.

The researchers suspect that calgranulin works by binding to the surface of the calcium oxalate crystal lattice where crystal growth takes place, thereby preventing the crystals from getting bigger or combining to form a large mass. Calgranulin may also prevent crystals from adhering to renal tubules in the kidneys, a prerequisite for the formation of kidney stones.

Pillay and colleagues are investigating how the subunits of calgranulin interact with each other, how calgranulin binds to calcium oxalate crystals, and ultimately, calgranulin's role in kidney stone formation.

The research was funded by the National Institutes of Health.