By Ed Susman, Contributing Writer, MedPage Today


Published: April 08, 2013
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner


ORLANDO – Patients who take topiramate (Topamax) therapy for treatment of migraine appear to deplete citrate in the urine, creating an environment for kidney stones, researchers reported here.

Within 30 days of the onset of topiramate therapy, mean urinary citrate excretion decreased 279 mg a day among the patients on the headache medication, reported Allan Jhagroo, MD, assistant professor of medicine at the University of Wisconsin in Madison, at the National Kidney Foundation 2013 Spring Clinical Meetings.

“Hypocitraturia from topiramate is rapid and progressive,” he told MedPage Today at his poster presentation. “This should be taken into account when starting therapy, particularly in patients with a history of urolithiasis or with identifiable lithogenic risk factors.”

“What surprised us,” Jhagroo added, “was that at 60 days the reduction in citrate output continued to progress.”

“The difference between baseline citrate levels and at 30 days was statistically significant” atP=0.001, he said, “even though we just had 12 people in this study. And the difference at 60 days compared with the 30-day figure was also statistically significant” at P=0.002.

The researchers noted that at 60 days, six of the seven patients who remained in the study and completed the 24-hour urinalysis were hypocitraturic, with a mean 196 mg/day of urinary citrate excretion.

Jhagroo said that citrate excretion of less than 320 mg a day clearly puts patients at risk for stone development. He said there is debate as to what level clinicians should strive to reach as a goal that removes people from risk. “I try to get people about 500 mg a day,” he said.

None of these patients had a history of kidney stones at the onset of the trial, nor did they develop stones while on topiramate during the study, Jhagroo said. They were stone-free also during the 6-to-12-month follow-up.

One patient was started on potassium citrate therapy of 30 mg/day and achieved a 102 mg/day increase in urinary citrate excretion within 2 weeks, the researchers noted, suggesting the treatment could be considered for adjunct therapy in some patients.

“Silence is a key feature in many aspects of kidney disorders; as such, there needs to be a greater awareness of the largely asymptomatic chronic kidney disease that affects approximately 13% of the U.S. population,” said Charmaine E. Lok, MD, medical director of the Renal Management and Hemodialysis Vascular Access programs at the University Health Network at Toronto General Hospital.

“However, one kidney disorder that can present quite dramatically is nephrolithiasis (kidney stones),” Lok, program chair of the meeting, told MedPage Today. “Passing a kidney stone can be quite painful and unforgettable.”

The clinical message from this study, Lok noted, is that “in those patients exposed to this drug with a previous history of kidney stones, or if they form a stone while on this drug, might benefit from 24-hour urine monitoring for hypocitraturia.”

“However, the study was small and should be explored in a larger prospective study to confirm its findings and to determine any clinical associations,” she cautioned.

The study was named as a National Kidney Foundation’s Outstanding Poster Presentation for 2013.

Jhagroo and Lok had no disclosures.



Primary source: National Kidney Foundation
Source reference:
Jhagroo R, et al “Topiramate Results in a Rapid and Progressive Decline in Urinary Citrate over 60 Days: A Prospective Study,” NFK 2013.


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