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

A 7-year-old boy with a history of febrile illness-related epilepsy syndrome presented with proteinuria and elevated creatinine. His severe epileptic disorder has been treated since age 2 with multiple antiepileptic medications, including valproic acid. More recently, he was noted to have features of Fanconi syndrome with acidosis, hypophosphatemia, hypokalemia, glucosuria, and nephrotic-range proteinuria. This was managed with supplements; however, in the setting of rising creatinine and prominent proteinuria, a kidney biopsy was performed. Renal cortex revealed markedly decreased expression of proximal tubule markers and increased expression of markers of distal nephron differentiation. Such findings have been described in several genetic and acquired conditions, including renal tubular dysgenesis, severe hypoxic injury following renal artery stenosis, and toxic injury related to in utero exposure to angiotensin-converting-enzyme inhibitors. Such changes have not been reported before in valproic acid-associated Fanconi syndrome, although in general, morphologic findings in this condition have not been well established in the literature.

Fanconi syndrome caused by antiepileptic therapy with valproic Acid.

PURPOSE: Valproic acid (VPA) is commonly used as an antiepileptic drug (AED). Regular screening for renal side effects is uncommon. Fanconi syndrome, a generalized dysfunction of renal proximal tubular cells, occurs with some inborn errors of metabolism. In addition, it can be acquired by exposure to several toxic substances. We report a case of Fanconi syndrome after long-term therapy with VPA. METHODS: An 8-year-old severely disabled and developmentally retarded boy with epilepsy was treated with VPA over a period of 7 years. He was hospitalized after a status epilepticus with laboratory findings suggesting a Fanconi syndrome. A PubMed-based worldwide review of the literature revealed that Fanconi syndrome is a rare side effect in children during long-term VPA treatment. We analyzed all 10 previously published cases by comparing age, underlying diseases, medication, and outcome. RESULTS: Examination revealed metabolic acidosis suggestive of renal tubular malfunction. Based on typical clinical and laboratory findings, an acquired Fanconi syndrome was diagnosed. This was treated with large doses of sodium bicarbonate. After discontinuation of VPA, renal function completely normalized within 2 months. CONCLUSIONS: Fanconi syndrome appears to be a rare but severe consequence of long-term VPA therapy. Therefore patients treated with VPA should be checked regularly for the possible development of VPA-induced Fanconi syndrome.