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

Area of Science:

• Nephrology
• Pharmacology
• Molecular Biology

Background:

• Omeprazole is a common proton pump inhibitor and anti-Helicobacter pylori medication.
• Its potential for causing kidney damage (nephrotoxicity) remains a subject of debate.

Purpose of the Study:

• To investigate the effects and underlying mechanisms of omeprazole on kidney cells and function.
• To assess omeprazole's impact on cell viability, gene expression, and inflammatory markers in kidney tissues.

Main Methods:

• In vitro studies using HK2, HPC, NRK, and 293T cells exposed to varying omeprazole concentrations.
• RNA sequencing to analyze gene expression changes in HK2 cells.
• In vivo studies involving animal models treated with omeprazole for 28 days.
• Histological analysis of kidney tissues to assess inflammation.

Main Results:

• Omeprazole induced concentration-dependent changes in cell morphology, density, and viability, with significant cell death at high concentrations (>50 μM).
• RNA sequencing revealed that 5 μM omeprazole inhibited genes related to proliferation, metabolism, and cytokine receptors in HK2 cells, increasing susceptibility to oxidative stress.
• Short-term animal studies (28 days) showed no significant adverse effects on body weight, organ weights, kidney/liver function, or levels of calcium and vitamin D.
• Tissue analysis indicated increased expression of the macrophage marker F4/80, suggesting an inflammatory response.

Conclusions:

• Therapeutic doses of omeprazole do not appear to cause clinically relevant nephrotoxicity in the short term.
• Omeprazole can disrupt gene expression, potentially reducing cell proliferation and viability.
• Long-term omeprazole use might increase kidney inflammation and susceptibility to environmental factors, warranting careful clinical consideration.