Topiramate is a novel neuromodulatory agent commonly prescribed for the treatment of seizure disorders and for migraine headache prophylaxis. Calcium phosphate kidney stones have been observed with topiramate treatment, but a comprehensive elucidation of stone-risk profile was not reported previously. This study explores the relationship between topiramate treatment and propensity for kidney stone formation. Methods: Thirty-two topiramate-treated subjects and 50 healthy volunteers participated in a cross-sectional study in which serum chemistry test and 24-hour urine collection results were evaluated for stone risk. Furthermore, a short-term longitudinal study was conducted in 7 patients to assess stone risk before and 3 months after topiramate treatment. Results: Serum 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 (737 ± 329 versus 278 ± 226 mg/d; P < 0.001). Net acid excretion did not change. The relative saturation ratio for brushite increased with topiramate treatment (3.14 ± 1.69 versus 1.27 ± 1.26; P < 0.001) because of urinary alkalinization and decreased urinary citrate levels. Urinary saturation of undissociated uric acid decreased (41 ± 52 versus 76 ± 60 mg/d; P < 0.001). Conclusion: 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 stones.

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