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 CKD patients undergoing CPB cardiac surgery, perioperative nitric oxide at 80 ppm intraoperatively and for 6 hours postoperatively reduced 7-day AKI, improved 6-month GFR, and decreased postoperative pneumonia without safety concerns. This randomized, sham-controlled trial supports NO conditioning as a renal-protective strategy.

Key Findings

• 7-day AKI incidence reduced: 23.5% (NO) vs 39.7% (control), RR 0.59 (95% CI 0.35–0.99; P=0.043).
• Higher GFR at 6 months: 50 vs 45 ml·min−1·1.73 m−2 (P=0.038).
• Lower postoperative pneumonia: 14.7% vs 29.4%, RR 0.5 (95% CI 0.25–0.99; P=0.039).
• Safety: methemoglobin/NO2− within acceptable ranges; no increase in oxidative-nitrosyl stress; no differences in transfusion, platelets, blood loss.

Clinical Implications

Cardiac surgery teams could consider perioperative NO (80 ppm intraop + 6h post) for CKD patients to lower AKI risk, with monitoring for methemoglobinemia and gas byproducts; multicenter validation is warranted.

Limitations

• Modest sample size and potential single-center context limit generalizability
• No detailed subgroup analyses by CKD stage or surgical complexity reported

Future Directions

Conduct multicenter RCTs to confirm efficacy, optimize NO dosing/duration, and evaluate effects across CKD stages and surgical types.