Abstracts

As a new anti-epileptic drug, topiramate (TPM) effectively treats multiple types of seizures in children; known adverse effects include cognitive deficits, and somnolence. Notably, in adult patients treated with this drug, nephrolithiasis is estimated to occur in 1.5% of patients (Wasserstein AG et al., [italic]Epilepsia[/italic] 1995; 36(Suppl 3): S153). However, the frequency of nephrolithiasis in [italic]children[/italic] on TPM is unknown. Additionally, little is known about the frequency of nephrocalcinosis in both children and adults treated with TPM. Possible mechanisms for nephrocalcinosis/ lithiasis include hypercalciuria and increased urinary bicarbonate(HCO[sub]3[/sub]) excretion from TPM[apos]s inhibitory effect on carbonic anhydrase.
We conducted a retrospective chart review of 40 consecutive children who initiated TPM therapy for seizures between January 1997 and February 2003. These children were followed periodically before and during TPM treatment with serum electrolytes, urinary calcium-to-creatinine (Ca/Cr) ratios, and renal ultrasonography.
22 children had baseline urinary Ca/Cr studies before the initiation of TPM. 17.5% (7 of 40 children) of children had hypercalciuria, defined as urinary Ca/Cr ratio [gt]0.21 (Stapleton FB et al., [italic]Pediatrics[/italic] 1982;69(5): 594-7). Three of 40 children (7.5%) with baseline hypercalciuria developed nephrocalcinosis/ lithiasis, necessitating discontinuation of TPM. An additional five children with baseline hypercalciuria did not progress to nephrocalcinosis/lithiasis. There was no statistically-significant difference in the mean urine Ca/Cr ratio, age at initiation of TPM therapy, or length of time on TPM between patients with nephrocalcinosis/lithiasis and those with hypercalciuria alone. Also, 31 children had baseline serum HCO[sub]3[/sub] levels before the initiation of TPM. The mean +/- SEM serum HCO[sub]3[/sub] level decreased from 24.3 mEq/L +/- 0.8 before TPM to 22.8 mEq/L +/- 0.8 at two to six months after initiation of therapy ([italic]p[/italic]= 0.047).
1) Hypercalciuria is a common finding in children starting TPM therapy for epilepsy.
2) Nephrocalcinosis/lithiasis occured in 7.5% of our patients taking TPM for seizures, as opposed to the 1.5% frequency of nephrolithiasis reported among adults on TPM. However, there is no medical literature regarding the incidence of [italic]nephrocalcinosis[/italic] in adults on TPM.
3) We observed a fall in serum HCO[sub]3 [/sub]levels after two to six months of TPM therapy, consistent with its inhibitory effect on carbonic anhydrase.
4) The long-term renal response to hypercalciuria and increased urinary HCO[sub]3[/sub] from TPM may be associated with nephrocalcinosis and/or nephrolithiasis in children taking this drug.