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.

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 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: David J Kennedy, W H Wilson Tang, Yiying Fan, Yuping Wu, Shirley Mann, Michael Pepoy, Stanley L Hazen
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 2 Issue 2 Pg. e000104 (Apr 04 2013) ISSN: 2047-9980 [Electronic] England
• PMID: 23557751 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Lipoproteins, HDL
• Aryldialkylphosphatase
• PON1 protein, human

Topics

• Aged
• Aged, 80 and over
• Antioxidants (physiology)
• Aryldialkylphosphatase (blood)
• Cardiovascular Diseases (enzymology, mortality, physiopathology)
• Case-Control Studies
• Dyslipidemias (physiopathology)
• Enzyme Assays
• Female
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Lipoproteins, HDL (physiology)
• Male
• Middle Aged
• Myocardial Infarction
• Oxidative Stress (physiology)
• Proportional Hazards Models
• Prospective Studies
• Renal Insufficiency, Chronic (enzymology, mortality, physiopathology)
• Stroke