Abstracts

RATIONALE: Zonisamide (ZNS) and topiramate (TPM) are antiepileptic drugs with carbonic anhydrase inhibition as one of their mechanisms of action. Carbonic anhydrase inhibitors are associated with increased risk for renal calculi. The ketogenic diet (KD) is a high fat, low carbohydrate diet, used to treat uncontrolled epilepsy. Urolithiasis is a reported side effect of the KD. The purpose of this analysis is to evaluate the incidence of urinary symptoms in a large group of pediatric patients receiving these treatments in combination or alone. At the end of this activity participants should have an appreciation of the risk of nephrolithiasis with selected new AEDs and the KD.
METHODS: Retrospective chart review was performed on all the pediatric patients seen in UCLA medical center for childhood epilepsy. 309 children receiving ZNS, TPM or the KD in various combinations or alone were identified. Data regarding the duration of treatment, medication doses and urinary side effect were collected and analyzed.
RESULTS: The patients[scquote] age ranged between 2 month to 21 years. 198 (64%) were treated with TPM, 23 (7.4%) with ZNS, and 15 (4.8 %) were on the KD. 29 (9.4%) were treated with TPM and ZNS together, 32 (10%) with TPM and KD, 7 (2.3%) with ZNS and KD, while 5 (1.6%) received TPM, ZNS and KD concurrently.
7 (2.3%) of the patients presented with dysuria and gross hematuria during the treatment. A work up revealed three UTIs, one (0.3%) hypercalciuria and three (0.97%) kidney stones or sludge as the cause. The hypercalciuric patient was on TPM (8mg/kg/day), ZNS (10 mg/kg/day) and KD concurrently. He did not develop nephrolithiasis at 1 year follow-up.
Of the three patients with kidney stones, one had multiple medical problems, and was admitted with dehydration; he was on a minimal dose of TPM (1 mg/kg/day). The second patient was on the KD, had prolonged limited fluid intake and was admitted with dehydration. After fluid intake was increased she remained borderline hypercalciuric without symptomatic stones. The third patient was on TPM (10 mg/kg/day). No follow up is available for him.
CONCLUSIONS: Although ZNS, TPM and the KD have been associated with increased risk of kidney stones, our analysis shows that the risk is minimal in the pediatric patient group . Only 1.3 % of the patients had kidney stones or hypercalciuria, 50% of them were severely ill and dehydrated. We conclude from our experience that it is safe to use these drugs/diet alone or in combination. Renal side effects can be reduced by increased fluid intake.
[Supported by: a Fellowship from the American Academy of Pediatrics to Shaunak Desai to undertake research with Dr. Sankar during the Summer of 2001.]; (Disclosure: Honoraria - Ortho-McNeil Pharmaceuticals Elan Pharmaceuticals)