Activation of paraoxonase 1 after hemodialysis is associated with HDL remodeling and its increase in the HDL2 fraction and VLDL.

Background: Paraoxonase 1 (PON1) activity is lower in renal failure patients. We hypothesize that part of the salutatory effect of hemodialysis on PON1 activity that we have previously found is due to HDL remodeling and shift of PON1 among HDL particles.

Methods: A total of 42 patients (18 females and 24 males, 63 ± 12 yr) on long-term HD, with a mean dialysis course of 6.4 yr (range 1-19 yr), were recruited. PON1 arylesterase and lactonase activities, PON1 and apolipoprotein distribution in HDL subclasses were measured by gel gradient electrophoresis and western blotting.

Results: The 3 different activities of PON1 we measured were significantly lower in patients as compared to control subjects; lactonase by 11%, triesterase by 19% and arylesterase by 20%, p<0.01. HDL increased slightly by 4.6%. LDL increased by 13% and VLDL decreased by 30%. These data are compatible with enhanced lipolysis of VLDL that is transformed into LDL. VLDL-PON1 activity increases significantly by 60%. PON1 activity increases by 16% in HDL2 whereas by this approach we could determine a 10% increase in the total area under the curve corresponding to total HDL. Changes in total lactonase activity were associated with changes in VLDL-PON1 and HDL2. In parallel with PON1 activation and shifts among particles, there are significant changes in apoE which increases notably in HDL2, paralleling the changes in PON1. No significant changes in apoAI or apoA-II the main structural HDL apolipoproteins were apparent after dialysis.

Conclusions: HD produces an activation of PON1 that can be predicted in part (30%) by efficiency of dialysis and in part (25%) by PON1 shifts to HDL2or VLDL (p<0.01). The removal of inhibitors and the change in the environment of PON1 in the micro-heterogeneity of HDL subclasses optimizes PON1 activity.