A Case of Severe Nonsteroidal Anti-Inflammatory Drug-Associated Acute Kidney Injury in a Patient with CYP2C9*2/*2: Lessons from the Vulture Crisis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a well-recognized cause of AKI, typically occurring in the setting of substantial exposure or predisposing risk factors. We report a case of severe AKI following minimal naproxen exposure in a previously healthy young adult. An 18-year-old man presented with abdominal and flank pain and was found to have KDIGO stage 3 AKI after receiving analgesic treatment for fracture-related pain. The patient had taken two oral 500-mg doses of naproxen seven days before presentation and had received two intravenous 2.5-g doses of metamizole, one on the day before and the other on the day of presentation. Clinical presentation, ultrasonography and magnetic resonance angiography argued against prerenal, postrenal and vascular causes. Suspected interstitial nephritis prompted empiric methylprednisolone therapy. Kidney biopsy revealed acute tubular injury without interstitial nephritis, and corticosteroids were discontinued. Kidney function recovered within two weeks of symptom onset. Given the severity of AKI relative to the reported drug exposure, pharmacogenetic testing was performed and revealed a CYP2C9*2/*2 genotype associated with reduced NSAID metabolism. Although the identified genotype is unlikely to fully account for the severe AKI observed, it may have contributed to the patient's susceptibility to nephrotoxicity. This case highlights pharmacogenetically impaired NSAID metabolism as a potentially underrecognized contributor to AKI and underscores the potential value of pharmacogenetic testing in selected patients without conventional risk factors.