Phenytoin Metabolite Renal Calculus: An Index Case

Abstract

Drugs and their metabolites are known factors in 1% to 2% of all kidney stones. Certain antiepileptic drugs are known to cause stone formation. Phenytoin is used as a first line antiepileptic therapy for many seizure disorders. We present what we believe to be the first report of a phenytoin metabolite urinary stone. A 79-year-old woman with a fever and seizure disorder was found to have a right pelvic kidney with hydronephrosis and multiple large calcifications. She had been taking the antiepileptic medication phenytoin for the past 10 years. Average total serum phenytoin level from the year prior was in the normal range. Free phenytoin levels were not routinely monitored, but the one value available was elevated at 5.1 ng/dL. The patient underwent a percutaneous nephrolitomy, ultimately expiring from medical complications after the procedure. Final stone analysis revealed a composition of 35% phenytoin metabolite (5-(para-hydroxyphenyl)-5-phenylhydantoin) and 65% proteinaceous material. An extensive review of literature including PubMed, MedLine, and various internet search engines was performed, searching for any prior reports of urinary calculi formed from phenytoin or its metabolite. No previous reports of phenytoin or phenytoin metabolite urinary stones were found in the medical literature. Phenytoin has many known ill effects on the genitourinary system including acute interstitial nephritis, nephrotic syndrome, acute renal failure, and priapism. Now we can add urinary lithiasis to the list of its potential adverse effects. This article represents the first report of a phenytoin metabolite urinary stone. A metabolite of the commonly used antiepileptic medication phenytoin can cause clinically relevant urolithiasis leading to significant morbidity and even mortality. Clinicians should have an increased level of suspicion for metabolite stone formation in symptomatic patients taking antiepileptic medications. Further studies on phenytoin metabolism and its potential for inducing urinary lithiasis should be performed.