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

  • Author(s): Suematsu, Yasunori
  • Goto, Masaki
  • Park, Christina
  • Nunes, Ane CF
  • Jing, WangHui
  • Streja, Elani
  • Rhee, Connie M
  • Cruz, Siobanth
  • Kashyap, Moti L
  • Vaziri, Nosratola D
  • Narayanaswami, Vasanthy
  • Kalantar-Zadeh, Kamyar
  • Moradi, Hamid
  • et al.
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 key component of HDL antioxidant activity. Apolipoprotein (Apo) A-I is the core HDL structural protein which plays a major role in various aspects of HDL function. OBJECTIVE:We sought to examine PON activity and Apo A-I levels in ESRD patients versus healthy controls. DESIGN AND SETTING:PON/Arylesterase activity was measured in 499 maintenance hemodialysis (MHD) patients and 24 healthy controls with similar distributions of age, sex and race/ethnicity. Serum acrolein-modified Apo A-I was measured in 30 MHD patients and 10 healthy controls. MAIN OUTCOME MEASURE(S):Multilevel Cox models were used to assess associations between PON activity, Apo A-I and HDL-C levels with 12-month all-cause mortality. RESULTS:PON activity was significantly lower in MHD patients versus controls. Furthermore, acrolein-modified Apo A-I levels were higher in MHD patients versus 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 to low PON and low Apo A-I was associated with lower mortality risk. CONCLUSIONS:In MHD patients, 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.

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