Remimazolam attenuates inflammation and kidney fibrosis following folic acid injury.

The transition of acute kidney injury (AKI) to chronic kidney disease (CKD) is characterized by intense inflammation and progressive fibrosis. Remimazolam is widely used for procedural sedation in intensive care units, such as AKI patients. Remimazolam has been shown to possess anti-inflammatory and organ-protective properties. However, the role of remimazolam in inflammation and renal fibrosis following AKI remains unclear. Here, we explored the effects of remimazolam on the inflammatory response and kidney fibrogenesis of mice subjected to folic acid (FA) injury. Our results showed that remimazolam treatment alleviated kidney damage and dysfunction. Mice treated with remimazolam presented less collagen deposition in FA-injured kidneys compared with FA controls, which was accompanied by a reduction of extracellular matrix proteins accumulation and fibroblasts activation. Furthermore, remimazolam treatment reduced inflammatory cells infiltration into the kidneys of mice with FA injury and inhibited proinflammatory or profibrotic molecules expression. Finally, remimazolam treatment impaired the activation of bone marrow-derived fibroblasts and blunted the transformation of macrophages to myofibroblasts in FA nephropathy. Additionally, the benzodiazepine receptor antagonist PK-11195 partially reversed the protective effect of remimazolam on the FA-injured kidneys. Overall, remimazolam attenuates the inflammatory response and renal fibrosis development following FA-induced AKI, which may be related to the peripheral benzodiazepine receptor pathway.