The effects of sodium valproate on the renal function of children with epilepsy

Abstract

Sodium valproate is one of the most commonly used drugs to treat epilepsy. However, there is growing evidence that valproate can cause renal tubular injury in children, and there are increasing reports of valproate-induced Fanconi's syndrome where the renal tubules lose their ability to reabsorb electrolytes, urea, glucose and protein. In this review article we attempt to bring together all of the studies conducted to date on the effects of valproate on renal function in epileptic children. The research is generally considered in two themes; the first comprises studies which indicate subclinical tubular injury measured by renal enzymes such as N-acetyl-β-D-glucosaminidase (NAG), and the second comprises clinical reports where Fanconi's syndrome has occurred. This article goes on to analyse the current data and draws on recurring patterns to suggest that a specific subpopulation of severely disabled epileptic children may benefit hugely from the close monitoring of enzymes which are indicative of renal tubular injury, particularly NAG or in the very least periodical urinalysis.

Kidney Biopsy Findings in a Patient With Valproic Acid-Associated Fanconi Syndrome

“…Certain factors including young age, nonambulatory state, and use of tube feedings appear to increase the risk of VA-associated FS. 4,5 The first report that includes a description of morphologic changes associated with VA toxicity was of a 12year-old boy with petit mal epilepsy, who developed muscle weakness and growth failure approximately 1 year after starting VA treatment; a kidney biopsy revealed giant mitochondria and abnormal granular cytoplasmic inclusions in PT cells. Discontinuation of VA led to immediate improvement.…”

“…Certain factors including young age, nonambulatory state, and use of tube feedings appear to increase the risk of VA-associated FS. 4,5…”

Acute Tubular Necrosis associated with the Ketogenic Diet in a Child with Intractable Epilepsy

“…Enlarged kidney size also returned to normal after stopping the KD. Although valproic acid has been asso ciated with renal Fanconi syndrome 12,13) , it may not be a direct cause in our case; as the blood levels were normal and it was taken persistently even after stopping the KD. It is hypothesized that an infectious condition might have contributed to initial dehydration findings with AKI in the present case.…”

Fanconi Syndrome Leading to Hypophosphatemic Osteomalacia Related to Tenofovir Use

“…Fanconi syndrome is a disorder of inadequate reabsorption of phosphorous, glucose and amino acids at the level of the proximal convoluted tubule. It can be caused by genetic conditions (cystinosis, fructose intolerance, galactosemia and glycogen storage diseases), drugs (including TDF, adefovir, cisplatin, ifosfamide, deferasirox and valproic acid) [8][9][10] and heavy metals such as lead, mercury and cadmium.…”