Biochemical and stone-risk profiles with topiramate treatment

Am J Kidney Dis. 2006 Oct;48(4):555-63. doi: 10.1053/j.ajkd.2006.07.003.

Abstract

Background: 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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acid-Base Equilibrium / drug effects
  • Acidosis / chemically induced
  • Acidosis / complications
  • Adult
  • Bicarbonates / blood
  • Bicarbonates / urine*
  • Calcium Phosphates / analysis
  • Citrates / urine
  • Cross-Sectional Studies
  • Female
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Fructose / pharmacology
  • Fructose / therapeutic use
  • Humans
  • Hydrogen-Ion Concentration
  • Kidney Calculi / chemically induced*
  • Kidney Calculi / drug therapy
  • Kidney Calculi / physiopathology
  • Kidney Calculi / urine*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neuroprotective Agents / adverse effects*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Topiramate

Substances

  • Bicarbonates
  • Calcium Phosphates
  • Citrates
  • Neuroprotective Agents
  • Topiramate
  • Fructose
  • calcium phosphate