Nitrite protects against cardiac surgery-associated acute kidney injury via inflammation suppression: insights from a rat cardiopulmonary bypass model

Abstract Cardiac surgery-associated acute kidney injury (CS-AKI) occurs in 20–30% of patients undergoing cardiac surgery and is associated with poor prognosis and increased healthcare burden. Despite its clinical importance, effective preventive strategies remain lacking due to the complex and poorly understood mechanisms involved. Nitrite, a nitric oxide donor active under hypoxic conditions, has shown organ-protective effects in preclinical studies, but its role in CS-AKI has not been investigated. In this study, we developed a rat model of cardiopulmonary bypass induced AKI and found that inflammation-related pathways, including TNF and NFκB signaling, were prominently activated. Pre-treatment with nitrite significantly reduced the expression of kidney injury markers and attenuated the activation of inflammation-related gene pathways. These findings highlight the contribution of inflammation to CS-AKI and suggest the therapeutic potential of nitrite for protecting kidney function during cardiac surgery.