Acute kidney injury following proton pump inhibitor therapy

A 63-year-old male with a past medical history significant for hypertension for 12 years, stage 3 chronic kidney disease (baseline serum creatinine concentration, 1.4mg/dl; estimated glomerular filtration rate, 54ml/min) secondary to hypertensive nephrosclerosis presented with generalized malaise and weakness for 2 weeks. He was referred for admission to the hospital for evaluation of renal dysfunction. Three months before this admission, he was treated with naproxen 500mg per day for bilateral knee pain owing to degenerative joint disease. After 2 weeks of therapy, he developed epigastric pain with anorexia, vomiting, and hematemesis. He underwent upper endoscopy, which revealed esophageal, gastric, and duodenal erosions and ulcerations. Serum creatinine concentration was 2.3mg/dl. Naproxen was discontinued, esomeprazole 40mg per day was initiated as anti-acid therapy and a liter of normal saline was administered intravenously. Two days later, the serum creatinine concentration returned to baseline (1.4mg/dl) and the patient was discharged home on esomeprazole and tramadol/ acetaminophen. On presentation to the hospital, blood pressure was 142/88mm Hg, pulse 100/min, temperature 98.9 degrees F, and respiratory rate 18/min. The conjunctivae were pale with anicteric sclera. Heart and lung examination was unremarkable except for a grade 1/6 systolic ejection murmur over the left sternal border. The abdomen had minimal epigastric tenderness, and there was trace edema in the ankles. There was no skin rash, petechiae, or purpura. Medications included amlodipine 10mg daily, esomeprazole 40mg daily, diazepam 2.5mg daily, tramadol/ acetaminophen 100mg twice daily, and calcitriol 1mcg every other day. Admission laboratory data are noted in Table 1. The remaining laboratory values, including liver function tests and coagulation profile were within normal range. There was no peripheral eosinophilia. Urinalysis was notable for specific gravity, 1.015; pH, 6.0; trace blood; 1+ protein; and trace leukocyte esterase. Examination of the urine sediment revealed 2 - 5 dysmorphic red blood cells/high-power field, 2 - 5 white blood cells/high-power field; few renal tubular epithelial cells; no cellular or granular casts were present. Urine eosinophils (Wright stain) were negative. Fractional excretion of sodium was 1.8% whereas spot urine protein/creatinine ratio was 0.65mg/g. A sonogram of kidneys demonstrated slightly echogenic but normal-sized kidneys without hydronephrosis. The patient was administered 2 Liters of normal saline and all medications except amlodipine were held. Despite this, the serum creatinine concentration rose the next day to 5.2mg/dl, whereas urine output was 550ml for the day. A kidney biopsy was performed for non-oliguric acute kidney injury.