Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKD: A Randomized Phase 2 Pilot Trial.

Randomized, phase 2 pilot trial in adults with predialysis chronic kidney disease, spanning stages 1 to 5, from the greater New Orleans area. The active intervention arm included 35 participants randomized to sodium nitrite plus isoquercetin.

Oral immediate-release sodium nitrite 40 mg twice daily plus isoquercetin 225 mg once daily for 12 weeks, taken at least 30 minutes before eating. The regimen was compared with matching placebo given on the same schedule.

The combination of sodium nitrite and isoquercetin did not significantly improve endothelial function or most biomarker outcomes versus placebo. Flow-mediated vasodilation changed by 1.1% at 12 weeks in the treatment group versus 0.3% with placebo, for a net change of 0.8% (95% confidence interval, 20.1 to 2.5). Changes in biomarkers of endothelial dysfunction, inflammation, and oxidative stress were not significantly different between groups. Safety was similar between groups, although leg swelling was more common in placebo. Overall, the findings do not support routine use of this combination on the basis of these results.

This was a small phase 2 pilot study with a 12 week follow-up, which limits power to detect modest effects and long-term outcomes. The single-center regional sample of adults with predialysis CKD also limits generalizability, and the biomarker findings were largely null despite exploratory subgroup hypotheses.