Renal Stones under Antiepileptic Treatment: Pathogenesis and Therapy

Renal stones are a side effect of treatment with carboanhydrase inhibitors (topiramate, zonisamide, sulthiame, and acetazolamide) as well as ketogenic diet. While especially ketogenic diet is used in pharmacoresistant epilepsy, the understanding of renal stone pathogenesis is basic successful therapy. Carboanhydrase inhibitors cause renal loss of bicarbonate leading to renal tubular acidosis and hypocitraturia. Urinary citrate forms complex with calcium, so hypocitraturia causes hypercalciuria, a lithogenic factor. Ketogenic diet mostly causes calcium oxalate stones. Due to high fat intake, intestinal fatty acids react with calcium saponification, disabled to form intestinal calcium oxalate. Free intestinal oxalate is resorbed and renally eliminated (hyperoxaluria type III) forming calcium oxalate stones. Besides this ketogenic diet may reveal hereditary lithogenic problems that are connected to vitamin substitution. Vitamine C is the main source of oxalate (hyperoxaluria type I + II). A normal substitution of vitamin D in a calcium hyperabsorber leads to hypercalciuria. In children, hereditary lithogenic factors should be included into diagnostic workup. The therapeutic consequence of hypocitraturia caused by carboanhydrase inhibitors is the substitution of citrate, correcting metabolic acidosis, normalizing hypocitraturia and hypercalciuria. In ketogenic diet, an oral substitution of calcium scavenges free oxalate forming intestinal calcium oxalate that cannot be resorbed. To monitor therapy, the determination of urinary calcium and oxalate excretion makes sense. Diagnosis, monitoring, and therapy will be demonstrated by case reports. The fundamental understanding of lithogenic factors caused by antiepileptic treatment represents the basis of a successful long-term treatment of severe epilepsies in childhood, particularly to avoid renal stone formation.