TY - JOUR
T1 - Omeprazole-induced acute interstitial nephritis
T2 - A possible Th1-Th17-mediated injury?
AU - Berney-Meyer, Linda
AU - Hung, Noelyn
AU - Slatter, Tania
AU - Schollum, John B.W.
AU - Kitching, A. Richard
AU - Walker, Robert J.
N1 - Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - IL-17
KW - Th1
KW - Th17
KW - eosinophils
KW - omeprazole-induced acute interstitial nephritis
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U2 - 10.1111/nep.12226
DO - 10.1111/nep.12226
M3 - Article
C2 - 24629073
AN - SCOPUS:84901048428
SN - 1320-5358
VL - 19
SP - 359
EP - 365
JO - Nephrology
JF - Nephrology
IS - 6
ER -