Urolithiasis on the ketogenic diet with concurrent topiramate or zonisamide therapy

Abstract

SummaryChildren with refractory epilepsy who are co-treated with the ketogenic diet (KD) and carbonic anhydrase inhibitor (CA-I) anti-epileptic medications including topiramate (TPM) and zonisamide (ZNS) are at risk for urolithiasis. Retrospective chart review of all children treated with ketogenic therapy at our institution was performed in order to estimate the minimal risk of developing signs or symptoms of stone disease. Children (N = 93) were classified into groups according to KD +/− CA-I co-therapy. Fourteen patients had occult hematuria or worse, including 6 with radiologically confirmed stones. Three of 6 calculi developed in the KD + ZNS group of 17 patients who were co-treated for a cumulative total of 97 months (3.1 stones per 100 patient months). One confirmed stone was in the KD + TPM group of 22 children who were co-treated for a cumulative total of 263 months (0.4 stones per 100 patient months). All six patients had at least three of five biochemical risk factors including metabolic acidosis, concentrated urine, acid urine, hypercalciuria and hypocitraturia. Standard of care interventions to minimize hypercalciuria, crystalluria and stone formation used routinely by pediatric nephrologists should also be prescribed by neurologists treating patients with combination anti-epileptic therapy. Non-fasting KD initiation, fluid liberalization, potassium citrate prophylaxis as well as regular laboratory surveillance are indicated in this high risk population.

Ketogenic diet guidelines for infants with refractory epilepsy

“…Uric acid, calcium oxalate, calcium phosphate or mixed composition stones have been reported in up to 7% of children on the KD [44][45][46]. Risk may be higher with long-term treatment [29] and concurrent use of carbonic anhydrase inhibitors [47]. The daily oral intake of citrate potassium that theoretically alkalinizes the urine and solubilizes urine calcium can be suggested to prevent kidney stones, in particular in the patients with cumulating risk factors.…”

Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy

“…[71] To avoid dose-related adverse effects in patients with renal disease, AEDs with predominantly renal excretion, such as GBP and TPM, should be avoided or used at low dosage. [77] Children with refractory epilepsy who are co-treated with the ketogenic diet and carbonic anhydrase inhibitor AEDs, such as TPM and ZNS, are at risk for urolithiasis. [77] …”

“…[77] Children with refractory epilepsy who are co-treated with the ketogenic diet and carbonic anhydrase inhibitor AEDs, such as TPM and ZNS, are at risk for urolithiasis. [77] …”

Nephrolithiasis associated with the use of topiramate in children

“…Stone formation has been noted within days to weeks of TPM treatment. 12 There is also evidence that TPM dose and duration might not directly correlate with stone formation. 4 Second, although USG is non-invasive and relatively accessible, parents/carers may be unwilling to perform investigations for screening purposes (ie when patients are asymptomatic).…”