Prevention of acute kidney injury by nitric oxide therapy in cardiac surgical patients: the role of nitrite and nitrate plasma levels
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Abstract
BACKGROUND: Acute kidney injury (AKI) from cardiopulmonary bypass (CPB)-associated hemolysis is one of the most common complications from cardiac surgery. Considerable effort has been done by many to reduce AKI occurrence through the use of inhaled nitric oxide (iNO) therapy. iNO has been shown to reduce instances of AKI following CPB by limiting the NO scavenging activities of free hemoglobin. Nitric oxide (NO) is quickly metabolized into nitrite and nitrate once in plasma and considerable evidence exists that these metabolites may be exploited to increase NO’s bioavailability further. This study aims to analyze the role plasma nitrite and nitrate concentrations play in reducing AKI in cardiac surgical patients treated with iNO during CPB.
METHODS: 250 patients were enrolled in a clinical trial at Massachusetts General Hospital. Patients were divided evenly and received 80 ppm iNO nitric oxide or placebo gas during CPB and the 24 hours following the procedure. Of the 250 patients, 50 evenly distributed between treatment and control groups were identified and enrolled in this ancillary study to measure plasma nitrite and nitrate levels through chemiluminescence assay.
RESULTS: Plasma nitrite and nitrate levels significantly increased in iNO-treated and placebo-treated patients 15 minutes, 24 hours, and 48 hours after CPB. No difference in AKI development or clinical biomarkers was found between the groups. CONCLUSION: Plasma nitrite and nitrate levels successfully measure iNO administration. Additionally, evidence of an increase in nitrite and nitrate concentration following iNO therapy suggests its role in increasing the molecule’s bioavailability, potential mechanism of action for systemic NO delivery, and potential for therapeutic manipulation.
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2025