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American Journal of Kidney Diseases

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

Published:December 04, 2016DOI:https://doi.org/10.1053/j.ajkd.2016.08.041

      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.

      Index Words

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      References

        • Saran R.
        • Li Y.
        • Robinson B.
        • et al.
        US Renal Data System 2014 Annual Data Report: epidemiology of kidney disease in the United States.
        Am J Kidney Dis. 2015; 66: S1-S305
        • Longenecker J.C.
        • Coresh J.
        • Powe N.R.
        • et al.
        Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: the CHOICE Study.
        J Am Soc Nephrol. 2002; 13: 1918-1927
        • Cheung A.K.
        • Sarnak M.J.
        • Yan G.
        • et al.
        Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients.
        Kidney Int. 2000; 58: 353-362
        • Himmelfarb J.
        • Stenvinkel P.
        • Ikizler T.A.
        • Hakim R.M.
        The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia.
        Kidney Int. 2002; 62: 1524-1538
        • Stenvinkel P.
        • Diczfalusy U.
        • Lindholm B.
        • Heimbürger O.
        Phospholipid plasmalogen, a surrogate marker of oxidative stress, is associated with increased cardiovascular mortality in patients on renal replacement therapy.
        Nephrol Dial Transplant. 2004; 19: 972-976
        • Himmelfarb J.
        • McMenamin M.E.
        • Loseto G.
        • Heinecke J.W.
        Myeloperoxidase-catalyzed 3-chlorotyrosine formation in dialysis patients.
        Free Radic Biol Med. 2001; 31: 1163-1169
        • Annuk M.
        • Zilmer M.
        • Lind L.
        • Linde T.
        • Fellström B.
        Oxidative stress and endothelial function in chronic renal failure.
        J Am Soc Nephrol. 2001; 12: 2747-2752
        • Ikizler T.A.
        • Morrow J.D.
        • Roberts L.J.
        • et al.
        Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients.
        Clin Nephrol. 2002; 58: 190-197
        • Rivara M.
        • Ikizler T.A.
        • Ellis C.
        • Mehrotra R.
        • Himmelfarb J.
        Association of plasma F2-isoprostanes and isofurans concentrations with erythropoiesis-stimulating agent resistance in maintenance hemodialysis patients.
        BMC Nephrol. 2015; 16: 79
        • Fessel J.P.
        • Jackson Roberts L.
        Isofurans: novel products of lipid peroxidation that define the occurrence of oxidant injury in settings of elevated oxygen tension.
        Antioxid Redox Signal. 2004; 7: 202-209
        • Alkazemi D.
        • Egeland G.M.
        • Roberts L.J.
        • Kubow S.
        Isoprostanes and isofurans as non-traditional risk factors for cardiovascular disease among Canadian Inuit.
        Free Radic Res. 2012; 46: 1258-1266
        • Ramos L.F.
        • Shintani A.
        • Ikizler T.A.
        • Himmelfarb J.
        Oxidative stress and inflammation are associated with adiposity in moderate to severe CKD.
        J Am Soc Nephrol. 2008; 19: 593-599
        • Mortensen S.A.
        • Rosenfeldt F.
        • Kumar A.
        • et al.
        The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial.
        JACC Heart Fail. 2014; 2: 641-649
        • Fotino A.D.
        • Thompson-Paul A.M.
        • Bazzano L.A.
        Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis.
        Am J Clin Nutr. 2013; 97: 268-275
        • Lim S.C.
        • Lekshminarayanan R.
        • Goh S.K.
        • et al.
        The effect of coenzyme Q10 on microcirculatory endothelial function of subjects with type 2 diabetes mellitus.
        Atherosclerosis. 2008; 196: 966-969
        • Hamilton S.J.
        • Chew G.T.
        • Watts G.F.
        Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients.
        Diabetes Care. 2009; 32: 810-812
        • Mehmetoglu I.
        • Yerlikaya F.H.
        • Kurban S.
        • Erdem S.S.
        • Tonbul Z.
        Oxidative stress markers in hemodialysis and peritoneal dialysis patients, including coenzyme Q10 and ischemia-modified albumin.
        Int J Artif Organs. 2012; 35: 226-232
        • Claessens A.J.
        • Yeung C.K.
        • Risler L.J.
        • Phillips B.R.
        • Himmelfarb J.
        • Shen D.D.
        Rapid and sensitive analysis of reduced and oxidized coenzyme Q10 in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and application to studies in healthy human subjects.
        Ann Clin Biochem. 2015; 53: 265-273
        • Milne G.L.
        • Gao B.
        • Terry E.S.
        • Zackert W.E.
        • Sanchez S.C.
        Measurement of F2- isoprostanes and isofurans using gas chromatography–mass spectrometry.
        Free Radic Biol Med. 2013; 59: 36-44
        • Morrow J.D.
        Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans.
        Arterioscler Thromb Vasc Biol. 2005; 25: 279-286
        • White I.R.
        • Royston P.
        • Wood A.M.
        Multiple imputation using chained equations: issues and guidance for practice.
        Stat Med. 2011; 30: 377-399
        • Rubin D.B.
        Multiple Imputation for Nonresponse in Surveys.
        Wiley-Interscience, Hoboken, NJ2004
        • Little R.J.
        • D’Agostino R.
        • Cohen M.L.
        • et al.
        The prevention and treatment of missing data in clinical trials.
        N Engl J Med. 2012; 367: 1355-1360
        • Hopke P.K.
        • Liu C.
        • Rubin D.B.
        Multiple imputation for multivariate data with missing and below-threshold measurements: time-series concentrations of pollutants in the Arctic.
        Biometrics. 2001; 57: 22-33
        • Madmani M.E.
        • Yusuf Solaiman A.
        • Tamr Agha K.
        • et al.
        Coenzyme Q10 for heart failure.
        Cochrane Database Syst Rev. 2014; 6: CD008684
        • Young J.M.
        • Florkowski C.M.
        • Molyneux S.L.
        • et al.
        A randomized, double-blind, placebo-controlled crossover study of coenzyme Q10 therapy in hypertensive patients with the metabolic syndrome.
        Am J Hypertens. 2012; 25: 261-270
        • Ferrante K.L.
        • Shefner J.
        • Zhang H.
        • et al.
        Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS.
        Neurology. 2005; 65: 1834-1836
        • Hyson H.C.
        • Kieburtz K.
        • Shoulson I.
        • et al.
        Safety and tolerability of high-dosage coenzyme Q10 in Huntington’s disease and healthy subjects.
        Mov Disord Off J Mov Disord Soc. 2010; 25: 1924-1928
        • Macunluoglu B.
        • Kaya Y.
        • Atakan A.
        • et al.
        Serum coenzyme Q10 levels are associated with coronary flow reserve in hemodialysis patients.
        Hemodial Int. 2013; 17: 339-345
        • Yeung C.K.
        • Billings F.T.
        • Claessens A.J.
        • et al.
        Coenzyme Q10 dose-escalation study in hemodialysis patients: safety, tolerability, and effect on oxidative stress.
        BMC Nephrol. 2015; 16: 183
        • Granata S.
        • Zaza G.
        • Simone S.
        • et al.
        Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease.
        BMC Genomics. 2009; 10: 1-13
        • Yazdi P.G.
        • Moradi H.
        • Yang J.-Y.
        • Wang P.H.
        • Vaziri N.D.
        Skeletal muscle mitochondrial depletion and dysfunction in chronic kidney disease.
        Int J Clin Exp Med. 2013; 6: 532-539
        • Eckardt K.-U.
        • Bernhardt W.W.
        • Weidemann A.
        • et al.
        Role of hypoxia in the pathogenesis of renal disease.
        Kidney Int Suppl. 2005; 99: S46-S51
        • Sluimer J.C.
        • Gasc J.-M.
        • van Wanroij J.L.
        • et al.
        Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis.
        J Am Coll Cardiol. 2008; 51: 1258-1265
        • Onur S.
        • Niklowitz P.
        • Jacobs G.
        • Lieb W.
        • Menke T.
        • Döring F.
        Association between serum level of ubiquinol and NT-proBNP, a marker for chronic heart failure, in healthy elderly subjects.
        Biofactors. 2015; 41: 35-43
        • Alehagen U.
        • Johansson P.
        • Björnstedt M.
        • Rosén A.
        • Dahlström U.
        Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.
        Int J Cardiol. 2013; 167: 1860-1866
        • Shults C.W.
        • Oakes D.
        • Kieburtz K.
        • et al.
        Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline.
        Arch Neurol. 2002; 59: 1541-1550
        • The Parkinson Study Group QE3 Investigators
        A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.
        JAMA Neurol. 2014; 71: 543-552
        • Morrow J.D.
        The isoprostanes: their quantification as an index of oxidant stress status in vivo.
        Drug Metab Rev. 2000; 32: 377-385
        • Kadiiska M.B.
        • Gladen B.C.
        • Baird D.D.
        • et al.
        Biomarkers of Oxidative Stress Study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?.
        Free Radic Biol Med. 2005; 38: 698-710
        • Montuschi P.
        • Barnes P.
        • Roberts L.J.
        Insights into oxidative stress: the isoprostanes.
        Curr Med Chem. 2007; 14: 703-717