Nitrite protects against cardiac surgery-associated acute kidney injury via inflammation suppression: insights from a...

Cardiac surgery-associated acute kidney injury (CS-AKI) is reported in 20-30% of patients undergoing cardiac surgery, leading to poor outcomes and increased healthcare costs. Because the pathophysiology of CS-AKI remains incompletely understood, no effective preventive strategies exist. Nitrite, a nitric oxide donor under hypoxic conditions, has been shown to exert organ-protective effects in various preclinical models. However, its protective effects against CS-AKI remain unexplored. This study aimed to generate a rat cardiopulmonary bypass (CPB) model to induce CS-AKI, identify the key molecular pathways involved in its pathophysiology, and evaluate the potential renoprotective effects of nitrite. A rat CPB model was established, and CS-AKI was confirmed through molecular and histological analyses. RNA-sequencing (RNA-seq) was performed to identify differentially expressed genes and enriched pathways. Nitrite (2 mg/kg) was administered before CPB, and its effects on kidney injury markers and inflammation-related pathways were evaluated. CS-AKI was successfully induced in our rat CPB model, as evidenced by increased KIM-1 and NGAL expression and renal histological damage. RNA-seq revealed activation of inflammation-related pathways, including the TNF and NFκB signaling pathways. Nitrite administration significantly reduced KIM-1 and NGAL expression and suppressed pathways associated with CS-AKI development. This study underscores the role of inflammation in the pathophysiology of CS-AKI and demonstrates that nitrite attenuates early tubular injury markers and inflammation-related pathways. These findings support further investigation of nitrite as a strategy to mitigate tubular injury during cardiac surgery.NEW & NOTEWORTHY This study demonstrates that nitrite administration attenuates early tubular injury in a rat cardiopulmonary bypass model of cardiac surgery-associated acute kidney injury. Nitrite attenuated early kidney injury markers and suppressed inflammatory signaling, including TNF-NFκB pathway activation. These findings provide mechanistic insight into nitrite-mediated attenuation of tubular injury and highlight nitrite administration as a potential therapeutic strategy for inflammation-driven renal injury during cardiopulmonary bypass.