Induction of Progressive Profound Hypocitraturia with Increasing Doses of Topiramate

Objectives: To provide prospective, longitudinal evidence of the effects of topiramate, an antiepileptic medication prescribed for migraine headaches, on stone-risk factors, specifically as pertaining to dosing and rapidity of onset. Methods: Patients scheduled to begin topiramate therapy were recruited to participate in the study. Enrolled subjects collected a pretreatment 24-hour urine specimen with subsequent 24-hour urine specimens collected 5 days after beginning topiramate and after each dose escalation. Results: Six subjects enrolled in the study, 4 of whom completed two additional urine collections after initiating topiramate therapy. The pretreatment urine collections of the 4 subjects with additional samples revealed the following mean (range) values: urine volume 1550 (1300 to 1900) mL, pH 6.75 (6 to 7), creatinine 1436.3 (1196 to 1590) mg/day, calcium 305.8 (209 to 423) mg/day, and citrate 606.8 (290 to 860) mg/day. Five days after initiation of topiramate, mean calcium decreased to 211.5 mg/day (31% decrease), and mean citrate decreased to 398 (99 to 804) mg/day, an average decrease of 39.8% (6.5% to 65.9%) per patient. After a dose escalation, calcium increased to 286.8 mg/day, but citrate decreased further to 209 (119 to 353) mg/day, an average decrease of 65.1% (57.9% to 71.7%) per patient from pretreatment levels. Conclusions: Topiramate therapy induces a profound decrease in urinary citrate levels, equivalent to the levels seen in distal renal tubular acidosis. Citrate levels decrease quickly after the start of topiramate therapy and continue to decrease with escalating doses.