Effect of Coenzyme Q10 on Biomarkers of Oxidative Stress and Cardiac Function in Hemodialysis Patients: The CoQ10 Biomarker Trial

doi:10.1053/j.ajkd.2016.08.041

American Journal of Kidney Diseases

Volume 69, Issue 3, March 2017, Pages 389-399

https://doi.org/10.1053/j.ajkd.2016.08.041 Get rights and content

Background

Oxidative stress is highly prevalent in patients with end-stage renal disease and is linked to excess cardiovascular risk. Identifying therapies that reduce oxidative stress has the potential to improve cardiovascular outcomes in patients undergoing maintenance dialysis.

Study Design

Placebo-controlled, 3-arm, double-blind, randomized, clinical trial.

Setting & Participants

65 patients undergoing thrice-weekly maintenance hemodialysis.

Intervention

Patients were randomly assigned in a 1:1:1 ratio to receive once-daily coenzyme Q₁₀ (CoQ₁₀; 600 or 1,200 mg) or matching placebo for 4 months.

Outcomes

The primary outcome was plasma oxidative stress, defined as plasma concentration of F₂-isoprotanes. Secondary outcomes included levels of plasma isofurans, levels of cardiac biomarkers, predialysis blood pressure, and safety/tolerability.

Measurements

F₂-isoprostanes and isofurans were measured as plasma markers of oxidative stress, and N-terminal pro−brain natriuretic peptide and troponin T were measured as cardiac biomarkers at baseline and 1, 2, and 4 months.

Results

Of 80 randomly assigned patients, 15 were excluded due to not completing at least 1 postbaseline study visit and 65 were included in the primary intention-to-treat analysis. No treatment-related major adverse events occurred. Daily treatment with 1,200 mg, but not 600 mg, of CoQ₁₀ significantly reduced plasma F₂-isoprostanes concentrations at 4 months compared to placebo (adjusted mean changes of −10.7 [95% CI, −7.1 to −14.3] pg/mL [P < 0.001] and −8.3 [95% CI, −5.5 to −11.0] pg/mL [P = 0.1], respectively). There were no significant effects of CoQ₁₀ treatment on levels of plasma isofurans, cardiac biomarkers, or predialysis blood pressures.

Limitations

Study not powered to detect small treatment effects; difference in baseline characteristics among randomized groups.

Conclusions

In patients undergoing maintenance hemodialysis, daily supplementation with 1,200 mg of CoQ₁₀ is safe and results in a reduction in plasma concentrations of F₂-isoprostanes, a marker of oxidative stress. Future studies are needed to determine whether CoQ₁₀ supplementation improves clinical outcomes for patients undergoing maintenance hemodialysis.

Section snippets

Study Design and Participants

This was a pilot, double-blind, parallel-group randomized clinical trial comparing daily CoQ₁₀ antioxidant therapy at 2 different doses (600 and 1,200 mg/d) with matching placebo. Study participants were recruited by study coordinators from outpatient dialysis facilities in the Seattle metropolitan area from September 2011 through April 2013. Criteria for study participation included the following: patients receiving thrice-weekly maintenance HD for at least 90 days, age older than 18 and

Participant Characteristics

Overall, participants had a mean age of 54 ± 13 (standard deviation) years; 22 (34%) were women, 17 (26%) were black, and 25 (40%) had diabetes (Table 1). More than 90% of participants dialyzed using an arteriovenous fistula. Patients assigned to receive 600 mg of CoQ₁₀ daily were younger, more likely to be black, and less likely to have diabetes compared with patients assigned to the placebo group. Patients assigned to receive 1,200 mg of CoQ₁₀ daily were less likely to be black and more likely to

Discussion

In this randomized, double-blind, placebo-controlled study of maintenance HD patients, daily CoQ₁₀ as antioxidant therapy was safe and well tolerated and resulted in a significant and dose-dependent increase in plasma CoQ₁₀ levels compared to placebo. In addition, CoQ₁₀ supplementation using a 1,200-mg daily dose significantly decreased plasma concentrations of F₂-isoprostanes, a robust plasma marker of oxidative stress. In the primary intention-to-treat analysis, there was no significant

Acknowledgements

The authors acknowledge Bret A. Lynch, Jerry Gillick, RPh, and Deb Schaller, RPh, for assistance with formulating and compounding the placebo wafer.

Support: This work was supported by grants from the National Institutes of Health, including the National Center for Complementary and Alternative Medicine R21 AT004265 and R21 AT3844, National Institute of Diabetes and Digestive and Kidney Diseases T32 DK007467 and K24 DK62849, National Center for Advancing Translational Sciences KL2 TR000421 and

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: Trial registration: www.ClinicalTrials.gov; study number: NCT01408680.

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Original InvestigationEffect of Coenzyme Q10 on Biomarkers of Oxidative Stress and Cardiac Function in Hemodialysis Patients: The CoQ10 Biomarker Trial

Background

Study Design

Setting & Participants

Intervention

Outcomes

Measurements

Results

Limitations

Conclusions

Section snippets

Study Design and Participants

Participant Characteristics

Discussion

Acknowledgements

Kidney Int

Kidney Int

Free Radic Biol Med

JACC Heart Fail

Am J Clin Nutr

Atherosclerosis

Free Radic Biol Med

Kidney Int Suppl

J Am Coll Cardiol

Int J Cardiol

Free Radic Biol Med

US Renal Data System 2014 Annual Data Report: epidemiology of kidney disease in the United States

Am J Kidney Dis

Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: the CHOICE Study

J Am Soc Nephrol

Phospholipid plasmalogen, a surrogate marker of oxidative stress, is associated with increased cardiovascular mortality in patients on renal replacement therapy

Nephrol Dial Transplant

Oxidative stress and endothelial function in chronic renal failure

J Am Soc Nephrol

Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients

Clin Nephrol

Association of plasma F2-isoprostanes and isofurans concentrations with erythropoiesis-stimulating agent resistance in maintenance hemodialysis patients

BMC Nephrol

Isofurans: novel products of lipid peroxidation that define the occurrence of oxidant injury in settings of elevated oxygen tension

Antioxid Redox Signal

Isoprostanes and isofurans as non-traditional risk factors for cardiovascular disease among Canadian Inuit

Free Radic Res

Oxidative stress and inflammation are associated with adiposity in moderate to severe CKD

J Am Soc Nephrol

Original Investigation
Effect of Coenzyme Q₁₀ on Biomarkers of Oxidative Stress and Cardiac Function in Hemodialysis Patients: The CoQ₁₀ Biomarker Trial