The Relationship between Nocturnal Enuresis and Sequential Changes of NAG/Morning Urine Gravity in Epileptic Children Treated with Valproate Sodium

Abstract

The aim of this study was to examine the presence of enuresis as an adverse effect of valproate sodium (VPA) and to prospectively evaluate renal tubular function in children receiving VPA as monotherapy and polytherapy. The study was conducted in 226 children. The patients were subdivided into the following four groups according to their therapy: VPA monotherapy as A; combination of VPA with other conventional antiepileptic drug (AED) therapy as B; and new AED administration after VPA therapy as C. To assess renal tubular function of all patient groups, urinary N-acetyl-β-glucosaminidase (NAG) levels and morning urine gravity were measured at baseline and after 2 weeks, 3 months, 6 months, and 1 year of treatment. Five (2.2%, A:B:C = 1:4:0) of 226 children presented with enuresis. Enuresis appeared at a median of 19 days after the beginning of therapy. All patients showed normal results on the urinary excretion of NAG through the study period; however, urinary NAG activity in the patients with enuresis was significantly higher than those without enuresis at 2 weeks (p = 0.0092), 3 months (p = 0.0097), and 6 months (p = 0.0021) of treatment with VPA. In contrast, morning urine gravity presenting with enuresis was significantly lower than that in the patients without enuresis after only 2 weeks of treatment (p = 0.035). The results of this study also revealed that VPA therapy does not always increase NAG excretion or decrease morning urine gravity. However, urinary NAG levels of reflected tubular function in the patients with enuresis were significantly higher than those in patients without enuresis. This change may have some effects on the development of enuresis.