Association of Serum Paraoxonase/Arylesterase Activity With All-Cause Mortality in Maintenance Hemodialysis Patients

J Clin Endocrinol Metab. 2019 Oct 1;104(10):4848-4856. doi: 10.1210/jc.2019-00334.

Abstract

Context: In end-stage renal disease (ESRD), serum high-density lipoprotein cholesterol (HDL-C) level is not an accurate predictor of mortality, partly because it does not necessarily correlate with indices of HDL function. Paraoxonase (PON) is a major enzyme constituent of HDL and a key component of HDL antioxidant activity. Apolipoprotein A-I (Apo A-1) is the core HDL structural protein that plays a major role in various aspects of HDL function.

Objective: We sought to examine PON activity and Apo A-I levels in patients with ESRD vs healthy controls.

Design and setting: PON/arylesterase activity was measured in 499 patients with maintenance hemodialysis (MHD) and 24 healthy controls with similar distributions of age, sex, and race/ethnicity. Serum acrolein-modified Apo A-I was measured in 30 patients with MHD and 10 healthy controls.

Main outcome measures: Multilevel Cox models were used to assess associations among PON activity, Apo A-I, and HDL-C levels with 12-month all-cause mortality.

Results: PON activity was significantly lower in patients with MHD vs controls. Furthermore, acrolein-modified Apo A-I levels were higher in patients with MHD vs controls. In fully adjusted models, high PON activity was associated with lower 12-month mortality, whereas no difference of mortality risk was observed across HDL-C levels. The combination of high PON and low Apo A-I compared with low PON and low Apo A-I was associated with lower mortality risk.

Conclusions: In patients with MHD, PON activity had a stronger association with 12-month mortality than HDL-C. Future studies are needed to examine the role of these markers as potential diagnostic and therapeutic tools in ESRD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein A-I / blood
  • Aryldialkylphosphatase / blood*
  • Biomarkers / blood
  • Carboxylic Ester Hydrolases / blood*
  • Case-Control Studies
  • Cause of Death
  • Cholesterol, HDL / blood
  • Cohort Studies
  • Female
  • Humans
  • Kidney Failure, Chronic* / blood
  • Kidney Failure, Chronic* / mortality
  • Kidney Failure, Chronic* / therapy
  • Male
  • Middle Aged
  • Renal Dialysis* / mortality
  • Survival Analysis

Substances

  • APOA1 protein, human
  • Apolipoprotein A-I
  • Biomarkers
  • Cholesterol, HDL
  • Carboxylic Ester Hydrolases
  • arylesterase
  • Aryldialkylphosphatase