Urolithiasis on the ketogenic diet with concurrent topiramate or zonisamide therapy

Abstract

Children 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.

Figure 1

Urolithiasis precipitated by anti-epileptic therapy in six KD patients. Therapeutic regimens for each of six patients listed on the y-axis are displayed graphically from the initiation of CA-I monotherapy at 0 month on the x-axis, until signs or symptoms of a calculus were noted in each patient. Each anti-epileptic agent is represented by a different colored bar, and co-therapy occurred whenever bars appear to overlap. Renal colic (RC), macroscopic hematuria (MH) and occult hematuria (OH) occurred anywhere from 1 day to 7 months after induction of ketosis.