title: Omeprazole-induced acute interstitial nephritis: a possible Th1-Th17-mediated injury?
abstract: BACKGROUND
  Omeprazole is an important cause of drug-induced acute interstitial nephritis (AIN). How omeprazole induces injury is unknown.
  
  
  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-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Medicine and Pathology, University of Otago, Dunedin, New Zealand; Microbiology and Immunology Department, Albert Einstein College of Medicine, New York, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Berney-Meyer
authors.forename: Noelyn
authors.initials: N
authors.lastname: Hung
authors.forename: Tania
authors.initials: T
authors.lastname: Slatter
authors.forename: John Bw
authors.initials: JB
authors.lastname: Schollum
authors.forename: A Richard
authors.initials: AR
authors.lastname: Kitching
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Walker
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D009853:Omeprazole / Q000009:adverse effects*; D054328:Proton Pump Inhibitors / Q000009:adverse effects; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D054328:Proton Pump Inhibitors; D009853:Omeprazole
keywords: IL-17; Th1; Th17; eosinophils; omeprazole-induced acute interstitial nephritis