Biochemical and stone-risk profiles with topiramate treatment.
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).


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 stones.
Welch
Brian J
BJ
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Graybeal
Dion
D
Moe
Orson W
OW
Maalouf
Naim M
NM
Sakhaee
Khashayar
K
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000138:Acidosis / Q000139:chemically induced / Q000150:complications; D000328:Adult; D001639:Bicarbonates / Q000097:blood / Q000652:urine*; D002130:Calcium Phosphates / Q000032:analysis; D002951:Citrates / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007669:Kidney Calculi / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000077236:Topiramate
D001639:Bicarbonates; D002130:Calcium Phosphates; D002951:Citrates; D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose; C020243:calcium phosphate