Omeprazole-induced acute interstitial nephritis: A possible Th1-Th17-mediated injury?

Linda Berney-Meyer, Noelyn Hung, Tania Slatter, John B.W. Schollum, A. Richard Kitching, Robert J. Walker

Research output: Contribution to journalArticle

19 Scopus citations

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-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. 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.

Original languageEnglish (US)
Pages (from-to)359-365
Number of pages7
JournalNephrology
Volume19
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • IL-17
  • Th1
  • Th17
  • eosinophils
  • omeprazole-induced acute interstitial nephritis

ASJC Scopus subject areas

  • Nephrology

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    Berney-Meyer, L., Hung, N., Slatter, T., Schollum, J. B. W., Kitching, A. R., & Walker, R. J. (2014). Omeprazole-induced acute interstitial nephritis: A possible Th1-Th17-mediated injury? Nephrology, 19(6), 359-365. https://doi.org/10.1111/nep.12226