title: Diminished antioxidant activity of high-density lipoprotein-associated proteins in chronic kidney disease.
abstract: BACKGROUND
  Decreased serum arylesterase activity, catalyzed by the high-density lipoprotein-associated paraoxonase (PON)-1, is associated with increased oxidant stress and atherosclerosis risk. We sought to determine the prognostic value of serum PON-1 activity, as monitored by PON or arylesterase activities, in subjects with chronic kidney disease (CKD), particularly in relation to established cardiac biomarkers.
  
  
  RESULTS
  Serum arylesterase and PON activities were measured in sequential subjects with CKD (n=630; estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m(2)) and an age- and sex-matched control group of non-CKD subjects (n=315) presenting for cardiac evaluations and prospectively followed for incident (3-year) major adverse cardiac events (composite of death, nonfatal myocardial infarction, and stroke). Serum arylesterase activity in CKD subjects was lower compared with that in non-CKD control subjects [median (interquartile range) 94 (77 to 112) versus 103 (85 to 121) μmol(L·min) per mL, P<0.001]; similarly, PON activity in CKD subjects was lower compared with that in non-CKD control subjects [median (interquartile range) 474 (275 to 936) versus 586 (301 to 1118) nmol(L·min) per mL, P<0.001]. Lower serum arylesterase (hazard ratio 1.8, 95% CI 1.26 to 2.57, P<0.01) was a predictor of poorer outcomes. After adjusting for traditional risk factors and medication use, lower serum arylesterase (hazard ratio 1.55, 95% CI 1.08 to 2.23, P<0.05) still conferred an increased risk of major adverse cardiac events at 3 years.
  
  
  CONCLUSIONS
  In patients with CKD, decreased serum arylesterase activity, a measure of diminished antioxidant properties of PON-1, predicts higher risk of incident long-term adverse cardiovascular events (heart attack, stroke, or death) in multivariable models adjusting for established clinical and biochemical risk factors.
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kennedy
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.forename: Yiying
authors.initials: Y
authors.lastname: Fan
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wu
authors.forename: Shirley
authors.initials: S
authors.lastname: Mann
authors.forename: Michael
authors.initials: M
authors.lastname: Pepoy
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000502:physiology*; D043303:Aryldialkylphosphatase / Q000097:blood*; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000401:mortality / Q000503:physiopathology; D016022:Case-Control Studies; D050171:Dyslipidemias / Q000503:physiopathology; D057075:Enzyme Assays; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008075:Lipoproteins, HDL / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction; D018384:Oxidative Stress / Q000502:physiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000201:enzymology* / Q000401:mortality / Q000503:physiopathology; D020521:Stroke
chemical_list: D000975:Antioxidants; D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
references.citation: Eur J Clin Invest. 2005 Apr;35(4):245-50
references.pmid: 15816993
references.citation: Clin Chem. 2005 Apr;51(4):719-28
references.pmid: 15684275
references.citation: J Am Soc Nephrol. 1998 Nov;9(11):2082-8
references.pmid: 9808094
references.citation: Nat Rev Nephrol. 2010 May;6(5):287-96
references.pmid: 20308998
references.citation: J Lipid Res. 2005 Jun;46(6):1239-47
references.pmid: 15772423
references.citation: Clin Chem Lab Med. 2011 Jan;49(1):61-7
references.pmid: 20961187
references.citation: Biochem Biophys Res Commun. 2008 Nov 7;376(1):105-10
references.pmid: 18762170
references.citation: Nephron Clin Pract. 2009;113(1):c46-53
references.pmid: 19602899
references.citation: Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266
references.pmid: 11904577
references.citation: Clin Biochem. 2010 Dec;43(18):1375-80
references.pmid: 20807524
references.citation: Free Radic Biol Med. 2004 Dec 15;37(12):1986-94
references.pmid: 15544917
references.citation: Lancet. 2000 Oct 7;356(9237):1213-8
references.pmid: 11072938
references.citation: Biofactors. 2009 Jan-Feb;35(1):98-104
references.pmid: 19319852
references.citation: Biochemistry. 2005 Apr 26;44(16):6371-82
references.pmid: 15835926
references.citation: Clin Chim Acta. 2007 Feb;377(1-2):213-20
references.pmid: 17118352
references.citation: J Lipids. 2012;2012:726048
references.pmid: 22523692
references.citation: Clin Nephrol. 2010 Feb;73(2):131-8
references.pmid: 20129020
references.citation: Cardiol Clin. 2005 Aug;23(3):319-30
references.pmid: 16084281
references.citation: Ther Apher Dial. 2010 Dec;14(6):572-6
references.pmid: 21118365
references.citation: Nature. 1998 Jul 16;394(6690):284-7
references.pmid: 9685159
references.citation: J Natl Med Assoc. 2011 Jun;103(6):524-33
references.pmid: 21830637
references.citation: Kidney Int Suppl. 2008 Dec;(111):S4-9
references.pmid: 19034325
references.citation: J Nephrol. 2004 Nov-Dec;17(6):813-8
references.pmid: 15593056
references.citation: Adv Exp Med Biol. 2010;660:113-27
references.pmid: 20221875
references.citation: J Lipid Res. 2009 Apr;50 Suppl:S195-200
references.pmid: 19033213
references.citation: Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):634-40
references.pmid: 20032289
references.citation: Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):516-22
references.pmid: 22075249
references.citation: Annu Rev Med. 2008;59:79-94
references.pmid: 17937591
references.citation: Clin Chim Acta. 2007 Sep;384(1-2):105-12
references.pmid: 17632094
references.citation: Semin Dial. 2009 Nov-Dec;22(6):636-43
references.pmid: 20017834
references.citation: Nephron. 1998 Oct;80(2):166-70
references.pmid: 9736814
references.citation: Atherosclerosis. 1998 Aug;139(2):341-9
references.pmid: 9712341
references.citation: Kidney Int. 2005 Jul;68(1):173-8
references.pmid: 15954906
references.citation: JAMA. 2008 Mar 19;299(11):1265-76
references.pmid: 18349088
references.citation: Clin Chim Acta. 2005 Feb;352(1-2):37-47
references.pmid: 15653099
references.citation: Trends Cardiovasc Med. 2005 Aug;15(6):212-9
references.pmid: 16182131
references.citation: Circulation. 2002 Jul 23;106(4):484-90
references.pmid: 12135950
references.citation: Kidney Int. 2002 Feb;61(2):705-16
references.pmid: 11849414
references.citation: Atherosclerosis. 2011 Nov;219(1):49-56
references.pmid: 21798540
references.citation: Hemodial Int. 2008 Oct;12(4):471-9
references.pmid: 19090870
references.citation: J Endocrinol. 2010 Feb;204(2):191-8
references.pmid: 19887391
references.citation: Clin Nephrol. 2002 Sep;58(3):190-7
references.pmid: 12356187
references.citation: J Am Soc Nephrol. 2007 Jan;18(1):16-28
references.pmid: 17167116
references.citation: Circ Heart Fail. 2011 Jan;4(1):59-64
references.pmid: 21062973
references.citation: Kidney Int. 2001 Jul;60(1):358-63
references.pmid: 11422772