LATE-ONSET OMEPRAZOLE-ASSOCIATED ACUTE INTERSTITIAL NEPHRITIS

Letter to the Editor: A 73-year-old woman presented to the emergency department with acute kidney injury and 3 to 4 weeks of general malaise consisting of headache, diffuse abdominal pain, myalgia, weakness, and subjective fever and chills. Her primary care physician sent her after laboratory results revealed a serum creatinine of 2.9 mg/dL (baseline 0.7 mg/dL) and a high erythrocyte sedimentation rate (ESR) of 93 mm/h. She had a history of monoclonal gammopathy of undetermined significance discovered 14 years before, but recent repeat serum protein electrophoresis (SPEP) showed disease resolution. Her medications include levothyroxine 100 μg once daily and omeprazole 20 mg once daily for the past 10 months to treat peptic ulcer disease. For occasional headaches, she took combination acetaminophen and caffeine. She was afebrile on physical examination, and her examination was unremarkable except for nontender bilateral forefinger bony enlargement in the distal interphalangeal joints. Her blood urea nitrogen level was 42 mg/dL, and creatinine was 3.5 mg/dL. Her electrolytes were within normal limits. Her white blood cell count was 9.1 × 109/L, hemoglobin 11.8 g/dL, hematocrit 34.7% with mean corpuscular volume 87 fL/cell, and platelets 430 × 109/L. Urinalysis was significant for more than 30 white blood cells, and a clean-catch urine culture showed no growth. Her ESR was 104 mm/h, and C-reactive protein (CRP) was 43.9 mg/L. SPEP showed two faint bands in the gamma region, but further characterization using immunofixation was negative. She was negative for antineutrophil cytoplasmic and antinuclear antibodies, double-strand deoxyribonucleic acid, and rheumatoid factor. Her complement component 3 was mildly high at 156 mg/dL (80–145 mg/dL reference range), and complement component 4 was normal. Tests for hepatitis, human immunodeficiency virus, respiratory syncytial virus, herpes, and parvovirus were negative. Within the first 24 hours of presentation to the emergency department, she received 2 L of normal saline. She was not given omeprazole during her hospital stay. Over the course of her stay, her serum creatinine continued to improve, from 3.5 mg/dL on admission to 1.9 mg/dL on discharge (daily creatinine: 3.5, 2.9, 2.5, 2.2, 2.1, 1.9 mg/dL). By hospital Day 5, the patient had experienced a gradual decline in creatinine to 2.1 mg/dL. The decision was made to perform a renal biopsy for definitive diagnosis. The biopsy showed diffuse lymphocytic infiltrate with numerous plasma cells and occasional eosinophils. The tubules showed mild acute injury with casts. Six glomeruli were present that showed mild mesangial hypercellularity. Vessels were unremarkable. According to electron microscopy, there was diffuse effacement of foot processes. Immunohistochemistry stains for herpes and adenovirus were negative. These results, in conjunction with the clinical presentation, were consistent with omeprazole-induced acute interstitial nephritis (AIN) and probably not due to her low-dose, infrequent acetaminophen use. Omeprazole was the first available drug in the class of proton pump inhibitors (PPIs), which suppress gastric acid secretion by inhibiting the H+/K+ATPase proton pump on parietal cell membranes. A review of English literature conducted in 2009 identified a total of 114 cases of PPI-induced AIN.1 The patient presented here was both typical and unique. As in most case reports, she was in her 70s and presented with insidious constitutional symptoms associated with acutely high creatinine that improved upon discontinuation of the agent. She also presented with sterile pyuria and high ESR and CRP, but she had no fever, rash, or urinary or peripheral eosinophilia, putting her among the 21% of patients who do not present with any of these signs or symptoms.2 Moreover, AIN typically develops within weeks of starting the PPI, as is expected of a hypersensitivity immune reaction. To the knowledge of the authors of this letter, there have been only two reported cases of omeprazole-induced AIN occurring after 10 or more months of use.3 In this case, late-onset omeprazole-associated AIN was arrived at as a biopsy-proven diagnosis of exclusion. Although the Food and Drug Administration has approved omeprazole for long-term use, clinicians should consider it as a possible cause of AIN even in patients who have tolerated the therapy for many months. Discontinuation of the drug leads to improvement. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: NN: conception and design, acquisition of data, drafting the letter, and final approval of the version to be published. GWM: acquisition, analysis, and interpretation of data; revising the letter critically for important intellectual content; and final approval of the version to be published. CK: conception and design, revising the letter critically for important intellectual content, and final approval of the version to be published. Sponsor's Role: None.