Potential Kidney Risks Associated With Clinical Doses of Omeprazole: In Vivo and In Vitro Studies

Omeprazole is a widely used proton pump inhibitor and anti-Helicobacter pylori drug; however, its nephrotoxicity has been controversial. This study aimed to explore the effects and mechanisms of omeprazole on the kidney. In HK2, HPC, NRK and 293 T cells, omeprazole-induced alterations in cell morphology, density and viability in a concentration-dependent manner. Excessively high concentrations (> 50 μM) led to a significant increase in cell death. Interestingly, NRK seemed insensitive to omeprazole. RNA sequencing revealed significant alterations in the genomic expression profile when HK2 cells were incubated at a concentration of 5 μM, including the inhibition of proliferative, metabolic and cytokine receptor gene expression. This alteration augments the environmental susceptibility of HK2 when exposed to H₂O₂. Animal studies have shown that omeprazole (10.4 mg/kg × day, 28 days) has no significant effect on body weight, kidney or heart weight or kidney or liver function, as well as plasma calcium and vitamin D. Tissue staining revealed increased expression of the macrophage marker F4/80 in response to omeprazole. In conclusion, therapeutic-dose omeprazole administration in the short term shows no clinically relevant nephrotoxicity. However, omeprazole decreases cell proliferation and viability by disrupting gene expression; thus, the long-term use of omeprazole may increase inflammation and environmental susceptibility. These findings provide valuable insights for the clinical use of omeprazole, highlighting the need for careful consideration of its effects in the kidney.