Urolithiasis with Topiramate and Zonisamide: Therapy? Prophylaxis?

Aims: A known side-effect of topiramate (TPM) anti-epileptic treatment is the formation of kidney stones with an incidence of 1–5.6% in adult patients. This effect may increase to 56% in young non-ambulatory patients. Under treatment with zonisamide (ZNS), kidney stones are 1–2% prevalent. The deposited kidney concrements are composed of either calcium phosphate or calcium oxalate. Pathophysiologically, inhibition of carboanhydrase activity by TPM or ZNS results in metabolic acidocis, hypocitraturia and elevated urine pH, conditions that favor stone deposition.

Methods: Retrospective analysis of clinical data of 4 patients on therapy with topiramate or zonisamide from November 2009 until December 2010.

Results:

gender, age (years)	epilepsy	ambulation	dosages (mg/kg)	co-medication	clinical manifestation	therapy
m, 3	sympt. focal (FCD)	yes	TPM; 6	-	Nephrocalcinosis type IIa (ultrasound)	dosage reduction, fluid intake
m, 4	generalized Dravet-S.	yes	TPM; 5,5 (seizure free)	-	sludge	Methionin, dosage reduction
m, 25	sympt. focal (Asyphyxia)	no	TPM; 8,5	CBZ, LEV, RUF	sludge	Dosage reduction
f, 6	sympt. focal (brain injury)	no	ZNS; 7,5	LEV, MES, ESM, VPA, Lyrica	kidney stone (ultrasound)	ZNS taken off before diagnosis

[Patients]

Discussion: There should be general information about kidney stones associated with therapy with TPM and ZNS including information about possible occurrence of urin-sludge and the need of sufficient fluid intake. Particularly for children with risc factors (e.g. with positive family history, urological or metabolic diseases, immobile or multi-morbid patients), undergoing co-medication with other carboanhydrase inhibitors (sultiame, acetozolamide) or on ketogenic diet urine analysis and kidney ultrasound checks should be performed. Beside dosage reduction and change in medication an acidification of urine or supplementation of citrate can be a therapeutic or prohylactic option.

In the case of all children with epilepsy – particularly with a physical handicap – we recommend information or training courses about healthy and dietetic nutrition.