Pembrolizumab and Nonsteroidal Anti-Inflammatory Drug (NSAID)-Induced Acute Tubular Necrosis and Acute Tubulointerstitial Nephritis: A Diagnostic and Therapeutic Challenge

Introduction: Acute interstitial nephritis (AIN) and acute tubular necrosis (ATN) are common causes of acute kidney injury (AKI) that can necessitate dialysis and are often precipitated by medications used for comorbidities. Case Description: Our patient is a 60-year-old female who presented with abnormal outpatient labs, including BUN 65, creatinine (Cr) 6.7, GFR 7, and Hb 7.6. She had a past medical history of hypertension and metastatic adenocarcinoma of the lung on maintenance therapy with pemetrexed and pembrolizumab. The chemotherapy was held one month prior, when she was admitted with AKI and acute pancreatitis. She continued taking lisinopril, despite being put on hold for low blood pressure. She had persistent periumbilical pain and left lower quadrant abdominal pain, and continued taking ibuprofen 800 mg three times/day. 2 months prior, Cr was 0.8; one month prior, Cr was 2. Initial lab values revealed- elevated Cr, low bicarbonate, high anion gap metabolic acidosis (HAGMA), and fractional urinary excretion of sodium (FeNa) 1.8%. CT was negative for stones or hydronephrosis. The nephrology service was consulted. IV fluids were started with lactated Ringer's and a bicarbonate drip for HAGMA. Serology workup was negative. Renal biopsy on light microscopy was consistent with acute tubular injury and acute tubulo-interstitial nephritis; no electron-dense deposits were seen on glomerular basement membrane or mesangium. There were no crescents, fibrinoid necrosis, or significant glomerular inflammation, and no evidence of fibrils to suggest amyloidosis. She was started on Prednisone 60 mg daily initially and increased to 75 mg daily. She was discharged with improved renal function and close nephrology follow-up was advised. Discussion: The most common cause of AIN is drug exposure. The classic presentation includes fever, rash, and eosinophilia. Identification and elimination of causative agents is a mainstay of treatment. This case underscores the importance of being vigilant for immune therapy-related interstitial nephritis, especially when other nephrotoxic drugs are co-administered.