Perioperative Nitric Oxide Conditioning Reduces Acute Kidney Injury in Cardiac Surgery Patients with Chronic Kidney Disease (the DEFENDER Trial): A Randomized Controlled Trial
In the DEFENDER trial, giving perioperative nitric oxide to chronic kidney disease patients undergoing cardiac surgery with cardiopulmonary bypass safely reduced postoperative acute kidney injury by about 40% and was associated with better kidney function at 6 months.
Background
Patients with CKD are especially vulnerable to acute kidney injury after cardiac surgery on cardiopulmonary bypass, partly because bypass-induced hemolysis depletes vascular nitric oxide. Effective pharmacologic prevention is lacking, motivating a test of perioperative nitric oxide.
Study design
Single-center randomized controlled trial of 136 CKD patients undergoing elective cardiac surgery with cardiopulmonary bypass, randomized 1:1 to 80 ppm nitric oxide intraoperatively and for 6 hours afterward, or sham. The primary outcome was AKI incidence within 7 days.
Key findings
AKI occurred in 23.5% of the nitric oxide group versus 39.7% of controls (relative risk 0.59, 95% CI 0.35–0.99; P=0.043). At 6 months, eGFR was higher with nitric oxide (50 vs 45 ml/min/1.73 m²; P=0.038), and postoperative pneumonia was less frequent (14.7% vs 29.4%; RR 0.5; P=0.039). Nitric oxide was safe — methemoglobin and nitrogen dioxide stayed within range, oxidative-nitrosyl stress did not rise, and bleeding/transfusion did not differ.
Clinical implications
Perioperative nitric oxide is a safe, inexpensive strategy that reduces cardiac-surgery-associated AKI and slows renal decline in CKD patients, supporting its consideration in this high-risk group — though as a single-center study, multicenter confirmation is needed (notably, a separate trial in patients with pre-existing endothelial dysfunction found no benefit).
Category
Research
Source
Anesthesiology
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