Perioperative Nitric Oxide Conditioning Reduces Acute Kidney Injury in Cardiac Surgery Patients with Chronic Kidney Disease (the DEFENDER-trial): a Randomized Controlled Trial

Background: Postoperative Acute kidney injury (AKI) is a significant concern for cardiac surgery patients with chronic kidney disease (CKD). Effective pharmacological interventions to mitigate these risks are urgently needed. This study aimed to evaluate the efficacy and safety of perioperative nitric oxide (NO) administration in preventing AKI and limiting CKD progression in patients undergoing cardiac surgery. Methods: A total of 136 patients with CKD undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) were randomized into two equal groups: the NO group (n=68), receiving 80 parts per million NO during the intraoperative period and for 6 hours post-surgery, and the control group (n=68), receiving a sham treatment. The primary outcome was AKI incidence within 7 days post-surgery. Results: AKI incidence was significantly lower in the NO group (16/68 patients, 23.5%) compared to the control group (27/68 patients, 39.7%) with a relative risk (RR) of 0.59 (95% CI 0.35–0.99; р=0.043). Six months post-surgery, the glomerular filtration rate was higher in the NO group (50 mL/min/1.73 m 2 [45; 54]) compared to the control group (45 mL/min/1.73 m 2 [41; 51], p=0.038). Postoperative pneumonia was significantly less frequent in the NO group: 10/68 (14.7%) vs 20/68 (29.4%) RR 0.5; (95% CI 0.25-0.99; р=0.039). NO administration was safe: methemoglobin and nitrogen dioxide levels remained within acceptable ranges, oxidative-nitrosyl stress did not increase, and there were no significant differences between the groups in blood transfusion requirements, platelet counts, or postoperative blood loss volumes Conclusions: Perioperative NO administration in CKD patients undergoing cardiac surgery with CPB is safe, reduces the incidence of AKI, and slows the progression of renal dysfunction.