First Reported Case of Naproxen-Induced Renal Cortical Necrosis

Drug-induced acute interstitial nephritis (AIN) is a well-recognized cause of acute kidney injury (AKI), commonly triggered by medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and proton pump inhibitors. Renal cortical necrosis (RCN), in contrast, is an uncommon cause of AKI resulting from prolonged and severe reduction in blood flow to the renal cortex. Although NSAIDs have previously been associated with several forms of kidney injury, reports of NSAID-related cortical necrosis are exceptionally rare.

In a case report published in the Indian Journal of Nephrology, Christine M. Jane and colleagues from the Department of Nephrology, Aster Medcity Hospital, Kochi, Kerala, described what they believe is the first reported case of renal cortical necrosis associated with naproxen use.

The case involved a 62-year-old man with poorly controlled type 2 diabetes, diabetic retinopathy, proteinuria, and hypertension who had taken naproxen 500 mg twice daily for one week to treat migraine. He later presented with fever, nausea, vomiting, breathlessness, bilateral flank pain, and leg swelling.

Investigations showed acute kidney injury with elevated serum creatinine, metabolic acidosis, electrolyte abnormalities, and marked eosinophilia. Imaging revealed mildly enlarged kidneys without obstruction. Although acute pyelonephritis was initially suspected and antibiotics were started, blood and urine cultures remained sterile, and extensive testing excluded infectious, autoimmune, vascular, and toxic causes. Despite treatment, renal function rapidly worsened, progressing to oligoanuric renal failure requiring hemodialysis.

Rising eosinophil counts prompted suspicion of a drug-induced reaction. A renal biopsy revealed patchy renal cortical necrosis along with eosinophilic inflammatory infiltrates and interstitial edema, confirming acute interstitial nephritis. No evidence of vasculitis, vascular obstruction, thrombotic microangiopathy, or immune complex disease was found.

Based on the clinical course, biopsy findings, and exclusion of other causes, the kidney injury was attributed to recent naproxen use.

The patient was treated with oral prednisolone and continued on dialysis. Kidney function gradually improved, with serum creatinine falling to 2.6 mg/dL, and dialysis was discontinued after six weeks. Steroids were subsequently tapered and stopped.

The authors highlighted that the coexistence of renal cortical necrosis and acute interstitial nephritis following NSAID exposure is exceptionally rare and stressed the importance of early recognition due to its potential impact on prognosis and management.