Omeprazole‐induced acute interstitial nephritis: A possible Th 1– Th 17‐mediated injury?

• Published in: Nephrology (Carlton, Vic.) Vol. 19; no. 6; pp. 359 - 365
• Main Authors: Berney‐Meyer, Linda, Hung, Noelyn, Slatter, Tania, Schollum, John BW, Kitching, A Richard, Walker, Robert J
• Format: Journal Article
• Language: English
• Published: 01.06.2014
• ISSN: 1320-5358; 1440-1797
• DOI: 10.1111/nep.12226

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 B anff 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 CD 4, CD 8, IL ‐17 A , IL ‐17 F , Foxp 3 and T ‐bet ( T cell subsets), CD 20 and CD 163 defined the cellular infiltrates. The predominant inflammatory cells were CD 4+ lymphocytic aggregates (77% of cases), combined with co‐staining of CD 4 IL and 17 A / F in 44–48% of all cases, suggesting a Th 17‐mediated inflammatory process. T ‐bet+ cell infiltrates were present to a lesser degree, suggesting additional Th 1 involvement. How omeprazole induces this inflammatory response is unclear, but may include direct effects by IL ‐17 expressing CD 4+ 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 Th 17 and Th 1 processes. Summary at a Glance In a renal biopsy series, the study examined the nature of interstitial infiltrates, mainly mononuclear in origin, and provided insights into a Th17‐mediated inflammatory process in omeprazole‐induced acute interstitial nephritis as distinct from the Th1 and Th2 networks.