Renal replacement therapy removes a large number of nitric oxide donors responsible for the nitrate–nitrite–nitric oxide pathway

Abstract

Backgrounds: Nitric oxide has a broad-spectrum antibacterial property promising as a new therapeutic agent for severe acute respiratory syndrome coronavirus-2 because nitric oxide donor (such as S-nitroso-N-acetylpenicillamine) reduces the replication of coronavirus-2. Patients with coronavirus disease 2019 undergoing dialysis generally have a higher mortality rate than the general population. Although the higher mortality rate in these patients may be related to their advanced age, it has been suggested that plasma nitrite and nitrate levels (products of nitric oxide metabolism) are significantly decreased after hemodialysis which may compromise the nitrate–nitrite–nitric oxide pathway and impair nitric oxide homeostasis. It results in increased cardiovascular mortality in patients undergoing dialysis. However, the profile of nitric oxide–producing substances is poorly understood during renal replacement therapy. Methods: We simulated continuous hemodialysis and hemodiafiltration to measure the amount of nitric oxide (nitric oxide-producing substance) clearance in vitro. Results: The results demonstrated increased nitric oxide clearance and higher clearance than creatinine (molecular weight: 113) and vitamin B12 (molecular weight: 1355) using highly efficient renal replacement therapy modes. Conclusion: The high nitric oxide clearance may have partly contributed to the high cardiovascular and coronavirus-2 mortality risk in patients on dialysis.