eneral Clinical Research Center.
Researchers found that taking topiramate on a long-term basis, or for about one year, caused systemic metabolic acidosis – a buildup of excessive acid in the blood – as a result of the inability of the kidney to excrete acid. Topiramate use also increased the urine pH and lowered urine citrate, an important inhibitor of kidney-stone formation.
“These changes increase the propensity to form calcium phosphate stones,” Dr. Sakhaee said.
In the short-term study, urinary calcium and oxalate – a chemical compound that binds strongly with calcium and is found in most calcium stones – did not significantly change in people taking topiramate.
Kidney stones are solid deposits that form in the kidneys from substances excreted in the urine. When waste materials in urine do not dissolve completely, microscopic particles begin to form and, over time, grow into kidney stones.
Before this study, the rate of kidney-stone formation with topiramate was reported as 1.5 percent. The low incidence rate may be an underestimation due to the short length of observation and the lack of ongoing kidney-stone surveillance and data collection for this drug, said Dr. Sakhaee, holder of the BeautiControl Cosmetics Inc. Professorship in Mineral Metabolism and Osteoporosis.
“There is a legitimate concern for the occurrence of kidney stones with long-term topiramate treatment,” said Dr. Sakhaee said. “Studies are needed to explore optimal measures to prevent kidney-stone formation with topiramate use.”
Other UT Southwestern researchers contributing to the study were Dr. Orson Moe, director of the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, Dr. Naim Maalouf, assistant professor of internal medicine and Dr. Brian J. Welch, a postdoctoral fellow in internal medicine.
The research was supported by the National Institutes of Health.
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