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- Title
Omeprazole-induced acute interstitial nephritis: A possible Th1- Th17-mediated injury?
- Authors
Berney‐Meyer, Linda; Hung, Noelyn; Slatter, Tania; Schollum, John BW; Kitching, A Richard; Walker, Robert J
- Abstract
Background Omeprazole is an important cause of drug-induced acute interstitial nephritis ( AIN). How omeprazole induces injury is unknown. Methods and Results 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-17 A, IL-17 F, 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 17 A/ 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. Conclusion 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.
- Subjects
INTERSTITIAL nephritis; KIDNEY diseases; OMEPRAZOLE; BENZIMIDAZOLES; PROTEINURIA
- Publication
Nephrology, 2014, Vol 19, Issue 6, p359
- ISSN
1320-5358
- Publication type
Article
- DOI
10.1111/nep.12226