Continuous Reduction of Plasma Paraoxonase Activity With Increasing Dialysis Vintage in Hemodialysis Patients

Plasma paraoxonase (PON) is an enzyme that hydrolyzes organic phosphate and aromatic carboxylic acid esters. Reduced activity is associated with early events of atherogenesis. The relevance of PON phenotypes is not well characterized in hemodialysis patients. In a cross-sectional study we measured PON activity in 377 hemodialysis patients photometrically using the substrates 4-nitrophenylacetate and phenylacetate. The PON ratio was calculated from 4-nitrophenylacetate-derived activity divided by phenylacetate-derived activity. Frequency distribution of the PON ratio showed three different PON phenotypes. 74% of hemodialysis patients showed PON phenotype 1, 21% PON phenotype 2, and 5% PON phenotype 3. Compared to hemodialysis patients with PON 1, patients with PON 2 or 3 showed higher conversion rates for 4-nitrophenylacetate. We observed a significant reduction of PON ratio with increasing dialysis vintage (P < 0.001 by ANOVA and post test for linear trend). In patients on hemodialysis treatment for less than 12 months, the PON ratio was 1.16 +/- 0.08 (n = 64). In patients on hemodialysis treatment for more than 60 months the PON ratio was 1.00 +/- 0.04 (n = 130; P = 0.05). This reduction of PON activity was due to reduced 4-nitrophenylacetate-derived PON activity with increasing dialysis vintage. In conclusion, plasma PON ratio significantly declines with increasing dialysis vintage.