High Incidence of Renal Stones in Severely Disabled Children with Epilepsy Treated with Topiramate

Abstract

Purpose This study was aimed to assess the accurate incidence of renal stones in severely disabled children treated with topiramate (TPM). Method We reviewed the medical records of severely disabled children with epilepsy under 15 years old who underwent radiological examinations to investigate urinary stones. The study enrolled 26 patients who were divided into two groups. One group had been treated with TPM for at least 1 year and the other had not been treated with TPM, zonisamide, acetazolamide, or other diuretic drugs. We collected parameters from the medical records and compared the groups. Results All participants were evaluated radiologically, with computed tomography (CT) in two patients, ultrasonography in 22 patients, and both in two. No patient had any morphological abnormality of the kidneys and history of urinary tract infection. There were no significant differences in sex, age, body weight, or feeding manner between the groups, while the incidence of renal stones or calcifications was significantly higher in the TPM-treated group (60 vs. 0%; p = 0.00241). Conclusion There is a high incidence of renal stone formation in severely disabled children treated with TPM.

Drug-Induced Urolithiasis in Pediatric Patients

“…Two studies tried to determine the accurate incidence of TPM-induced urolithiasis in the pediatric population through comparing the incidence of urolithiasis between children with disability using TPM for management of refractory epilepsy versus a control group of similar children not using TPM. They showed similar results, with an incidence of urolithiasis significantly higher in the TPM group versus the no TPM group (60% vs 0% and 54.6% vs 0%) [86,87]. Furthermore, an open-label extension study from two studies (phase 1 and phase 3) in 284 infants < 2 years old with refractory partial-onset seizures treated with TPM (only 135 infants completed the open-label extension study) was published in 2011 and showed that one of the treatmentemergent adverse events found was nephrolithiasis in 18 of the 135 patients (13.3%) [93].…”

“…Thus, TPM has become one of the most frequently prescribed drugs in the USA, ranking among the top 50 most prescribed drugs [85]. TPM has been long known for its lithogenic effect through the metabolic changes induced by this drug [86][87][88][89][90][91][92][93]. A systematic review published in 2013 showed that the overall annual incidence of symptomatic nephrolithiasis with TPM usage was 2.1% [94]; however, the incidence of nephrolithiasis in the pediatric population ranged from 4.2% to 60% (Table 3).…”

“…A systematic review published in 2013 showed that the overall annual incidence of symptomatic nephrolithiasis with TPM usage was 2.1% [94]; however, the incidence of nephrolithiasis in the pediatric population ranged from 4.2% to 60% (Table 3). It is worth mentioning that the high incidence of 60% may be explained by the presence of other risk factors for urolithiasis as this study was performed in non-ambulatory children, a population in which there are increases in bone resorption, which subsequently leads to hypercalcemia and hypercalciuria [86].…”

“…Interestingly, TPM may cause an increase in bicarbonate loss through the gastrointestinal tract (mostly due to diarrhea). These metabolic alterations cause metabolic acidosis, elevated urinary pH, hypocitraturia, and hypercalciuria and, subsequently, an increase in the risk of calcium stone formation [83,86]. Dell'Orto et al [94] demonstrated in their systematic review a significant tendency towards metabolic acidosis, where the circulating bicarbonate was significantly lower in TPM patients compared to control subjects; however, this finding was not significantly related to the dose of TPM.…”

“…Dell'Orto et al [94] demonstrated in their systematic review a significant tendency towards metabolic acidosis, where the circulating bicarbonate was significantly lower in TPM patients compared to control subjects; however, this finding was not significantly related to the dose of TPM. In this review, few studies reported the urinary pH and the calcium/ creatinine ratio, and these ranged from 6.8-8.07 [86,87] and 0.22-0.30 [87,89], respectively. Generally, the relation between TPM administration and stone formation should be interpreted with caution, as stone composition was not analyzed in most of the patients reported in the literature and the causal relationship was based only on the duration between the stone event and the start of medication.…”