Effects of a mitochondrial-targeted ubiquinol on vascular function and exercise capacity in chronic kidney disease: a randomized controlled pilot study

Mitochondria-derived oxidative stress has been implicated in vascular and skeletal muscle abnormalities in chronic kidney disease (CKD). The purpose of this study was to investigate the effects of a mitochondria-targeted ubiquinol (MitoQ) on vascular function and exercise capacity in CKD. In this randomized controlled trial, 18 patients with CKD (means ± SE, age: 62 ± 3 yr and estimated glomerular filtration rate: 45 ± 3 mL/min/1.73 m2) received 4 wk of 20 mg/day MitoQ (MTQ group) or placebo (PLB). Outcomes assessed at baseline and follow-up included macrovascular function measured by flow-mediated dilation, microvascular function assessed by laser-Doppler flowmetry combined with intradermal microdialysis, aortic hemodynamics assessed by oscillometry, and exercise capacity assessed by cardiopulmonary exercise testing. Compared with PLB, MitoQ improved flow-mediated dilation (baseline vs. follow-up: MTQ, 2.4 ± 0.3% vs. 4.0 ± 0.9%, and PLB, 4.2 ± 1.0% vs. 2.5 ± 1.0%, P = 0.04). MitoQ improved microvascular function (change in cutaneous vascular conductance: MTQ 4.50 ± 2.57% vs. PLB −2.22 ± 2.67%, P = 0.053). Central aortic systolic and pulse pressures were unchanged; however, MitoQ prevented increases in augmentation pressures that were observed in the PLB group (P = 0.026). MitoQ did not affect exercise capacity. In conclusion, this study demonstrates the potential for a MitoQ to improve vascular function in CKD. The findings hold promise for future investigations of mitochondria-targeted therapies in CKD. NEW & NOTEWORTHY In this randomized controlled pilot study, we investigated the effects of a mitochondria-targeted ubiquinol (MitoQ) on vascular function and exercise capacity in chronic kidney disease. Our novel findings showed that 4-wk supplementation of MitoQ was well tolerated and improved macrovascular endothelial function, arterial hemodynamics, and microvascular function in patients with stage 3–4 chronic kidney disease. Our mechanistic findings also suggest that MitoQ improved microvascular function in part by reducing the NADPH oxidase contribution to vascular dysfunction.
This article was originally published in American Journal of Physiology - Renal Physiology. The version of record is available at: https://doi.org/10.1152/ajprenal.00067.2023. Copyright © 2023 the American Physiological Society. This article will be embargoed until 10/01/2024.
chronic kidney disease, mitochondria, oxidative stress, vascular function
Kirkman, Danielle L., Joseph M. Stock, Ninette Shenouda, Natalie J. Bohmke, Youngdeok Kim, Jason Kidd, Raymond R. Townsend, and David G. Edwards. “Effects of a Mitochondrial-Targeted Ubiquinol on Vascular Function and Exercise Capacity in Chronic Kidney Disease: A Randomized Controlled Pilot Study.” American Journal of Physiology-Renal Physiology 325, no. 4 (October 1, 2023): F448–56. https://doi.org/10.1152/ajprenal.00067.2023.