Omeprazole‐induced acute interstitial nephritis: A possible Th1–Th17‐mediated injury?. Issue 6 (June 2014)

• Record Type: Journal Article
• Authors: Berney‐Meyer, Linda; Hung, Noelyn; Slatter, Tania; Schollum, John BW; Kitching, A Richard; Walker, Robert J
• Is Part Of: Nephrology. Volume 19:Issue 6(2014)
• Page Start: 359
• Page End: 365
• Publication Date: 2014-06
• Subjects: Nephrology -- Periodicals; Kidneys -- Diseases -- Periodicals; Nephrologists -- Periodicals; 616.61; 616.61
• DOI: 10.1111/nep.12226
• Languages: English
• ISSNs: 1320-5358

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="nep12226-sec-0001" sec-type="section"> <title>Background</title> <p>Omeprazole is an important cause of drug‐induced acute interstitial nephritis (AIN). How omeprazole induces injury is unknown.</p> </sec> <sec id="nep12226-sec-0002" sec-type="section"> <title>Methods and Results</title> <p>Detailed clinical assessment of 25 biopsy‐proven cases of omeprazole‐induced AIN showed that all patients presented with impaired renal function, sterile pyuria with varying amounts of proteinuria but no eosinophiluria and no systemic symptoms to suggest a vasculitis. Histological analyses were characteristic of an acute tubulitis with an inflammatory cellular infiltrate. Using modified Banff scheme criteria, mild tubulitis (t1) was present in 56% of cases, a moderate tubulitis (t2) in 24% of cases, and a severe tubulitis in 20% of cases. Most (78%) of cases had mononuclear cell infiltrates, no significant eosinophilic infiltrates were found, and glomeruli were not involved. Immunostaining for CD4, CD8, IL‐17A, IL‐17F, Foxp3 and T‐bet (T cell subsets), CD20 and CD163 defined the cellular infiltrates. The predominant inflammatory cells were CD4+ lymphocytic aggregates (77% of cases), combined with co‐staining of CD4 IL and 17A/F in 44–48% of all cases, suggesting a Th17‐mediated inflammatory process. T‐bet+ cell infiltrates were present to a lesser degree, suggesting additional Th1 involvement. How omeprazole induces this inflammatory response is unclear, but may include direct effects by IL‐17 expressing CD4+ cells on renal tubular cells.</p> </sec> <sec id="nep12226-sec-0003" sec-type="section"> <title>Conclusion</title> <p>This large biopsy series of omeprazole‐induced AIN demonstrates the features of acute tubulitis, with significant interstitial infiltrates consistent with immunopathological Th17 and Th1 processes.</p> </sec> </abstract>