Abstract 16926: The Effects of a Mitochondrial Targeted Ubiquinone (MitoQ) on Vascular Function in Chronic Kidney Disease

Abstract

Introduction: Aberrant vascular function contributes to the substantially high cardiovascular burden of chronic kidney disease (CKD). Mitochondrial derived oxidative stress is a potential therapeutic target to ameliorate CKD related vascular dysfunction. Hypothesis: We hypothesized that a mitochondrial targeted antioxidant (MitoQ) would improve vascular function in Stage 3-5 CKD patients without overt cardiovascular disease. Methods: In this controlled, double-blind trial, 18 CKD patients (Mean±SEM: Age, 62±3 years; eGFR, 45±3 ml•min•1.73 2 ) were randomized to receive an oral dose of MitoQ (20mg/day; MTQ) or a Placebo (PLB) for 4 weeks. Outcome measures were assessed at week 0 and week 4. Aortic pressure waves were synthesized from brachial artery waveforms acquired by oscillometry and the use of a generalized transfer function. The central pressure waveform was separated into forward and reflected waves using a triangular flow waveform. Conduit artery vascular function was assessed via brachial artery flow mediated dilation (FMD). Results: MitoQ was well tolerated and patient compliance was high (MTQ, 99.6±0.4%; PLB, 97.8±2.2%). Independent of peripheral (Baseline vs. Follow Up: MTQ, 140±6 vs. 137±6 mmHg; PLB, 136±4 vs. 134±6 mmHg; interaction p=0.7) and central (MTQ, 128±5 vs. 123±6 mmHg; PLB, 124±3 vs. 123±5 mmHg; interaction p=0.8) systolic blood pressures, MitoQ maintained forward wave amplitudes (MTQ, 31±3 vs. 29±1 mmHg; PLB, 29±3 vs. 36±3 mmHg; interaction p=0.05) and tended to reduce reflected wave amplitudes (MTQ, 18±2 vs. 16±1 mmHg; PLB, 19±2 vs. 21±2 mmHg; interaction p=0.04). MitoQ administration favored improvements in FMD (MTQ, 2.4±0.3 vs. 4.0±0.9%; PLB, 4.2±1.0 vs. 2.5±1.0%; interaction p=0.04). Conclusions: These results suggest that targeting mitochondrial derived reactive oxygen species holds promise as a potential therapeutic strategy to improve CKD related vascular dysfunction. Whether MitoQ related improvements in arterial hemodynamics are a result of augmented cardiac function or a reduction in vascular resistance warrants future investigation in larger studies.