INTRODUCTION: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery performed under cardiopulmonary bypass (CPB). Patients with chronic kidney disease (CKD) are particularly vulnerable to cardiac surgery-associated AKI. Nitric oxide (NO) has great potential for implementing multi-organ protection in cardiac surgery. OBJECTIVES: To test the hypothesis that perioperative nitric oxide conditioning has a good safety profile and reduces the incidence of acute kidney injury during cardiac surgery under cardiopulmonary bypass in patients with chronic kidney disease. MATERIAL AND METHODS: An interim analysis of the results of the single-center prospective randomized controlled trial DEFENDER was conducted. Currently, the study included 96 patients with CKD who underwent cardiac surgery under CPB. Patients was randomized into 2 equal groups consisting of 48 people each. In the experimental group, during the operation and 6 hours after it, 80 ppm NO was delivered through the ventilator and CPB circuits. In the control group, during the operation and 6 hours after it, a standard oxygen-air mixture without NO was delivered through the ventilator and CPB circuits. The end points of the study were: the difference between groups in the incidence of AKI, the incidence of postoperative complications, outcomes and the safety profile of NO therapy. RESULTS: In the experimental group, the incidence of AKI was significantly lower compared to the control group (16,7 и 35,4 %, p = 0.036). In the experimental group, nitrogen dioxide concentration in the gas-air mixture and methemoglobin level were not above the reference range. The groups did not differ in the frequency of blood transfusions, the amount of postoperative bleeding, or the number of platelets on the first day after surgery. CONCLUSIONS: Perioperative nitric oxide conditioning has a good safety profile and reduces the incidence of acute kidney injury during cardiac surgery with CPB in patients with chronic kidney disease.