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Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic

Chrysan J Mohammed1, Yanmei Xie1, Pamela S Brewster1

  • 1Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.

Journal of Clinical Medicine
|July 18, 2019
PubMed

Insights

Paraoxonase (PON)-1 lactonase activity, not protein levels, predicts adverse clinical outcomes in chronic kidney disease (CKD) patients. Lower PON-1 activity indicates a higher risk, highlighting its prognostic value beyond traditional factors.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Cardiovascular disease (CVD) burden is high in chronic kidney disease (CKD), exceeding traditional risk factor predictions.
  • Diminished paraoxonase (PON)-1 activity correlates with increased oxidant stress, a key factor in CKD pathogenesis.

Purpose of the Study:

  • To evaluate the prognostic significance of circulating PON-1 protein and PON lactonase activity for adverse clinical outcomes in CKD patients.
  • To compare PON-1 levels and activity between CKD patients and healthy controls across different CKD stages.

Main Methods:

  • Simultaneous measurement of circulating PON-1 protein levels and PON lactonase activity in CKD patients and non-CKD subjects.
  • Analysis of prognostic value of PON-1 parameters for adverse clinical outcomes, adjusted for traditional risk factors.

Main Results:

  • CKD patients exhibited significantly lower circulating PON-1 protein levels and PON lactonase activity compared to non-CKD controls.
  • Circulating PON lactonase activity, but not protein levels, independently predicted future adverse clinical outcomes in CKD.
  • The best survival outcomes were associated with lower circulating PON-1 protein levels combined with higher PON-1 activity within CKD subjects.

Conclusions:

  • Diminished circulating PON lactonase activity is a significant predictor of adverse clinical outcomes in CKD patients.
  • PON-1 protein levels alone do not predict outcomes, but combined with activity, offer prognostic insights.
  • PON-1 lactonase activity serves as a valuable prognostic biomarker for cardiovascular risk in CKD.

Keywords:
chronic kidney diseaseclinical outcomeslactonase activityparaoxonase

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