THE SERUM PARAOXONASE ACTIVITY IN PATIENTS WITH CHRONIC-RENAL-FAILUREAND HYPERLIPIDEMIA

Human serum paraoxonase is physically associated with an apolipoprotei n (Apo-A(1)) and clusterin-containing high-density lipoprotein (HDL) a nd prevents low-density lipoprotein from lipid peroxidation. The aim o f our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidem ic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase acti vity and polymorphism in 119 hemodialyzed uremic patients, 107 patient s with primary hyperlipoproteinemia, and in 110 healthy control subjec ts. The serum paraoxonase activity was significantly decreased both in hyperlipidemic (p < 0.01) and uremic patients (p < 0.001) as compared with controls. On comparison, the serum paraoxonase activity was sign ificantly lower (p < 0.001) in uremic than in hyperlipoproteinemic pat ients. The HDL and Apo-A(1) levels were as follows: uremic < hyperlipi demic < control. To assess whether the observed reduction in paraoxona se activity was due to HDL and Apo-A(1) level decreases, we standardiz ed the enzyme activity for HDL and Apo-A(1) concentrations. We found t hat the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients(103.3 +/- 69.5) as compared with hyp erlipidemic patients (137.64 +/- 81.0) and controls (194.45 +/- 94.45) . The standardized values for Apo-A(1) showed a similar tendency: para oxonase/Apo-A(1) ratio in uremic patients 89.64 +/- 47.8, in hyperlipi demic patients 128.12 +/- 69.83, and in controls 161.40 +/- 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change si gnificantly in the patient groups. These results suggest that HDL conc entration and phenotypic distribution of paraoxonase may not be the on ly determining factors, but that other as yet undetermined factors cou ld be involved in the enzyme activity changes.