Research links high zinc levels, kidney stones

Kidney stones are hard, often jagged masses of crystalized minerals that form in the kidney. Some kidney stones are very small and pass through the body without even being noticed. Larger stones may get stuck in the urinary tract, however, causing severe pain and blood in the urine.

According to the National Institutes of Health (NIH), kidney stones are one of the most common disorders of the urinary tract, affecting nearly 10 percent of the U.S. population. Each year in the U.S., people suffering with kidney stones make over a million visits to health care providers, including over 300,000 visits to emergency rooms due to the pain. While kidney stones are more common in adults, they also are becoming increasingly common in infants, children, and teenagers from all races and ethnicities.

"Nearly 90 percent of kidney stones are calcium-based, but we really don't know what causes those stones to form," says Dr. Killilea. "In the past, urologists recommended limiting the amount of calcium in the diet to help prevent the formation of kidney stones, but that did not turn out to be very useful. So we wanted to learn what other factors might contribute to the formation of kidney stones."

The lead author of the study, Thomas Chi, MD, an assistant professor of medicine in the UCSF Department of Urology, approached Buck Institute researchers to participate in the study because of their experience in using fruit flies to model various diseases. Dr. Chi also approached Dr. Killilea to participate in the study because of his expertise in minerals.

The first step was to recognize what others had taken for granted.

"Years ago, researchers noticed that fruit flies produced little crystal 'granules' in their primitive kidney-like structures, but that finding had been mostly ignored," Dr. Killilea explains. "Only recently have we found that these granules are similar in some ways to kidney stones in people. Fruit flies are easily managed in the laboratory, and we can manipulate their genetics and diet. We started screening the genes that might play a role in calcification, and we came across a gene that plays a role in metabolizing zinc. At the same time, I was analyzing the fly granules to see what was in them, and I found relatively high levels of zinc. The way these results came together was a nice surprise!"

Dr. Killilea stresses that the results of the study are still new, so it is too early to know about the impact of zinc levels on human kidney stone formation.

"This study's results do not mean that zinc is bad for you-in fact, quite the opposite," he says. "Zinc is an essential element in the human diet. It is well known that people with a zinc deficiency have immune systems that don't function as well, and that might make kidney stone disease worse. It is only very high levels of zinc that might be a problem.

With the fruit flies, large doses of zinc caused them to produce stones faster and to produce bigger stones. People should not avoid zinc, but we need to determine what the optimal levels of zinc might be, especially in people at risk for stone disease. That information might eventually give us tools to treat or even prevent kidney stone formation."

According to Dr. Killilea, a number of other factors can also contribute to an increased risk for developing kidney stones, including stress, inflammation, lack of exercise, obesity, and dehydration. Children in particular may be sensitive to dietary influences, such as the consumption of sugary drinks. "An increased consumption of sugary drinks can contribute to both obesity and dehydration," he notes. "Sugary drinks are loaded with 'empty calories' and also can be dehydrating."

The NIH confirms that the prevalence of kidney stones has been rising in the U.S. over the past 30 years. Researchers observe that many kidney specialists have reported seeing more children with kidney stones in recent years. In fact, a study published in the November 2014 issue of The Journal of Urology® by researchers at Children's Hospital of Philadelphia showed that the incidence of kidney stones in children has increased by approximately 6 to 10 percent over the past 25 years. Kidney stones that form during childhood have a similar composition to those that form in adulthood, the study noted.

"We really need more research on kidney stone development in children," Dr. Killilea says. "Growing children need an adequate amount of zinc to stay healthy, but there has not been a lot of work on figuring out what level of zinc is too high."

Some general recommendations for preventing kidney stones-for both children and adults-include staying hydrated, limiting salt intake, and avoiding sugary or caffeinated beverages.

"This study was a very big project that would have been nearly impossible to complete without the collaboration among UCSF, CHORI, and the Buck Institute," Dr. Killilea notes. "The affiliation of UCSF Benioff Children's Hospital Oakland, CHORI, and UCSF in San Francisco has promoted more projects where we can collaborate on research and services to benefit children's lives in the San Francisco Bay Area."