Diminished Antioxidant Activity of High-Density Lipoprotein-Associated Proteins in Chronic Kidney Disease

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. methods and 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 m2) 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. © 2013 the authors. published on behalf of the american heart association,inc.,by wiley-blackwell.