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

Summary

In 136 CKD patients undergoing cardiac surgery with CPB, perioperative inhaled NO (80 ppm intraoperatively and for 6 h postoperatively) reduced AKI incidence (23.5% vs 39.7%; RR 0.59) and improved 6-month GFR, with fewer postoperative pneumonias and an acceptable safety profile.

Key Findings

• AKI incidence reduced from 39.7% (control) to 23.5% (NO); RR 0.59 (95% CI 0.35–0.99; P=0.043).
• Higher 6-month GFR in NO group (median 50 vs 45 ml·min−1·1.73 m−2; P=0.038).
• Lower postoperative pneumonia with NO (14.7% vs 29.4%; RR 0.5; P=0.039) and no increase in methemoglobin, NO2, or bleeding/transfusion metrics.

Clinical Implications

Consider perioperative NO (80 ppm) during and shortly after CPB in CKD patients to reduce AKI risk and preserve renal function, while monitoring methemoglobin and NO2. Implementation requires NO delivery capability and multidisciplinary protocols.

Limitations

• Modest sample size with confidence intervals near unity for primary outcome
• Single or limited center setting and specific CKD/CPB population may limit generalizability

Future Directions

Large multicenter trials to confirm efficacy, define optimal dosing/duration, identify responder subgroups, and evaluate cost-effectiveness and implementation at scale.