Nephrolithiasis and Nephrocalcinosis From Topiramate Therapy in Children With Epilepsy

Abstract

IntroductionAdults treated with topiramate may develop nephrolithiasis, but its frequency in children on topiramate is unknown. Topiramate inhibits renal carbonic anhydrase, which can lead to renal tubular acidosis and hypercalciuria. We studied 40 consecutive children who initiated topiramate therapy for seizures between January 1997 and February 2003, followed for a mean of 36 months.MethodsSerum electrolytes, urinary calcium/creatinine ratios, and renal ultrasonography were performed before topiramate and every 6 months thereafter.ResultsFour children developed nephrolithiasis and/or nephrocalcinosis, which resolved on discontinuation of topiramate. In 40 patients, the mean urinary calcium/creatinine ratio increased over time (P < 0.001). The mean serum bicarbonate in 40 patients decreased over time (P < 0.01). Twenty-three children had urinary calcium/creatinine ratios before topiramate. Nine children with baseline hypercalciuria (defined as urinary calcium/creatinine >0.21) were compared with the 14 children with baseline normal urinary calcium excretion. A greater increase in urinary calcium/creatinine ratios occurred in hypercalciuric children (P < 0.001) and a greater decrease in serum bicarbonate levels occurred in the hypercalciuric children (P < 0.05) compared with children with baseline normal calcium excretion. Greater urinary calcium excretion was associated with increasing doses of topiramate (P = 0.039).ConclusionOur study shows that long-term therapy with topiramate in children is associated with persistent hypercalciuria and metabolic acidosis, which can lead to nephrocalcinosis and/or nephrolithiasis. All children initiating topiramate therapy should have baseline and follow-up urinary calcium/creatinine studies, serum electrolytes, and periodic renal ultrasonography, if the urinary calcium/creatinine ratio increases to a level above normal for age.

La Nefrocalcinosis: una patología no tan infrecuente.

“…Otros fármacos como los corticoides o el topiramato, se asocian con nefrocalcinosis, sobre todo en edad pediátrica. También, existen varios casos en la literatura científica que hablan de la relación entre el fracaso renal agudo, hiperfosfaturia severa, y nefrocalcinosis y la toma de preparaciones intestinales de fosfato sódico para procedimientos endoscópicos o cirugías intestinales [2,8,12,13,17,21]. Posiblemente los mecanismos implicados en el desarrollo de la nefrocalcinosis tras el consumo de estos fármacos son la producción de alteraciones metabólicas similares a las que aparecen en la acidosis tubular renal distal tipo 1, dando lugar a una acidificación de la orina por la reabsorción residual de bicarbonato, provocándose un estado de hipocitraturia que favorece la formación de depósitos de fosfato cálcico [12,13,[21][22][23].…”

Drug-Induced Urolithiasis in Pediatric Patients

“…Thus, TPM has become one of the most frequently prescribed drugs in the USA, ranking among the top 50 most prescribed drugs [85]. TPM has been long known for its lithogenic effect through the metabolic changes induced by this drug [86][87][88][89][90][91][92][93]. A systematic review published in 2013 showed that the overall annual incidence of symptomatic nephrolithiasis with TPM usage was 2.1% [94]; however, the incidence of nephrolithiasis in the pediatric population ranged from 4.2% to 60% (Table 3).…”

A incidência de nefrolitíase em pacientes que fazem terapia com Topiramato: uma revisão de literatura/ The incidence of nephrolithiasis in patients undergoing Topiramat therapy: a literature review

“…Dentre os efeitos adversos manifestados em pacientes que fazem uso do Topiramato à longo prazo, pode-se mencionar a nefrolitíase. A estrutura do TPM é semelhante à do fármaco acetazolamida, visto que ambos possuem a função de inibir a anidrase carbônica, efeito que promove falha na reabsorção de bicarbonato, que causa alcalinização da urina e leva a um quadro de supersaturação de fosfato de cálcio e nefrolitíase [6]. O objetivo dessa revisão de literatura é procurar identificar estudos, em determinados bancos de dados, que evidenciem a incidência de cálculos renais nos indivíduos das diversas faixas etárias que realizam terapia com TPM à longo prazo, além de comparar os estudos mais antigos com os atuais relacionados a esse assunto.…”