Topiramate (Topamax) is a neuronal stabilizing agent (aka anticonvulsant medication) that is FDA-approved for and prescribed for headache and Migraine prevention.

Researchers at the University of Texas Southwestern Medical Center at Dallas (UT Southwestern) have have completed a study showing that topiramate can increase the propensity for calcium phosphate kidney stones. Although there has been anecdotal evidence of this potential side effect and much discussion of it, this is the first study to formally investigate the issue and examine the mechanism of stone formation.

"The wide-spread and escalating use of topiramate emphasizes the importance of considering the long-term impact of this drug on kidney-stone formation," said Dr. Khashayar Sakhaee, senior author of the study and chief of mineral metabolism at UT Southwestern.
 

Study methods

This was a two-phase study:

Phase 1: Thirty-two patients treated with topiramate and 50 healthy volunteers participated in a cross sectional study.  Serum chemistry test (panel of blood tests) and 24-hour urine collection results were evaluated for kidney stone risk.

Phase 2: A short-term study was conducted in seven patients treated with topiramate to assess stone risk before and 3 months after Topamax treatment.
 

Study results

The following differences were measured in the blood and urine tests:

• Serum (blood) bicarbonate levels were lower with topiramate treatment.
• Urinary pH, urinary bicarbonate excretion, and fractional excretion of bicarbonate increased, whereas urinary citrate excretion was significantly lower.
• Net acid excretion did not change.
• The relative saturation ratio for brushite increased with topiramate treatment because of urinary alkalinization and decreased urinary citrate levels.
• Urinary saturation of undissociated uric acid decreased.
    

Study conclusions

Treatment with topiramate causes systemic metabolic acidosis, markedly lower urinary citrate excretion, and increased urinary pH. These changes increase the propensity to form calcium phosphate kidney stones.

To date, the reported incidence of kidney stones while taking topiramate has been 1.5%. The reason for this low rate of incidence may be underestimation due to the shorter duration of trials and studies and the lack of ongoing observation for kidney stones and data collection for topiramate.
  

Summary

In addition to the anecdotal evidence we had prior to this study, we now have clinical study date demonstrating that long-term use of topiramate increases the propensity for kidney stones. Dr. Sakhee commented,

"There is a legitimate concern for the occurrence of kidney stones with long-term topiramate treatment... Studies are needed to explore optimal measures to prevent kidney-stone formation with topiramate use."

If you are considering taking topiramate, please discuss this issue with your doctor, especially if you have a history of kidney stones or any problems with kidney function.

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Resources:

Welch, Brian J.. MD; Graybeal, Dion, MD; Moe, Orson W., MD; Maalouf, Naim M., MD; Sakhee, Khashayar, MD. "Biochemical and Stone-Risk ProfilesWith Topiramate Treatment." Am J Kidney Dis 48:555-563. doi:10.1053/j.ajkd.2006.07.003.

Newswise. "Drug Prescribed for Migraines and Seizures Increases Risk of Kidney Stones." October 31, 2006.

Published October 31, 2006
© Teri Robert