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

Autor:	Chen J; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana.; Department of Medicine, Southeast Louisiana Veterans Health Care System, New Orleans, Louisiana., Hamm LL; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana., Bundy JD; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana., Kumbala DR; Renal Associates of Baton Rouge, Baton Rouge, Louisiana., Bodana S; Department of Nephrology, Ochsner Health System, New Orleans, Louisiana., Chandra S; Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania., Chen CS; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana., Starcke CC; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana., Guo Y; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana., Schaefer CM; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana., Lustigova E; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana., Mahone E; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana., Vadalia AM; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana., Livingston T; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana., Obst K; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana., Hernandez J; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana., Bokhari SR; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana., Kleinpeter M; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana., Alper AB; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana., Lukitsch I; Department of Nephrology, Ochsner Health System, New Orleans, Louisiana., He H; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana., Nieman DC; Human Performance Lab, Appalachian State University, Kannapolis, North Carolina., He J; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.; Tulane University Translational Science Institute, New Orleans, Louisiana.
Jazyk:	angličtina
Zdroj:	Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2020 Nov 06; Vol. 15 (11), pp. 1566-1575. Date of Electronic Publication: 2020 Oct 06.
DOI:	10.2215/CJN.02020220
Abstrakt:	Background and Objectives: Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD. Design, Setting, Participants, & Measurements: This randomized, double-blind, placebo-controlled phase 2 pilot trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted. Results: Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF- α , IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups. Conclusions: This randomized phase 2 pilot trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD. Clinical Trial Registry Name and Registration Number: Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888. (Copyright © 2020 by the American Society of Nephrology.)
Databáze:	MEDLINE
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