The Serum Paraoxonase Activity in Patients with Chronic Renal Failure and Hyperlipidemia

Abstract

Human serum paraoxonase is physically associated with an apolipoprotein (Apo-A₁) and clusterin-containing high-density lipoprotein (HDL) and prevents low-density lipoprotein from lipid peroxidation. The aim of our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidemic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase activity and polymorphism in 119 hemodialyzed uremic patients, 107 patients with primary hyperlipoproteinemia, and in 110 healthy control subjects. 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 significantly lower (p < 0.001) in uremic than in hyperlipoproteinemic patients. The HDL and Apo-A₁ levels were as follows: uremic < hyperlipidemic < control. To assess whether the observed reduction in paraoxonase activity was due to HDL and Apo-A₁ level decreases, we standardized the enzyme activity for HDL and Apo-A₁ concentrations. We found that the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients (103.3 ± 69.5) as compared with hyperlipidemic patients (137.64 ± 81.0) and controls (194.45 ± 94.45). The standardized values for Apo-A₁ showed a similar tendency: paraoxonase/Apo-A₁ ratio in uremic patients 89.64 ± 47.8, in hyperlipidemic patients 128.12 ± 69.83, and in controls 161.40 ± 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change significantly in the patient groups. These results suggest that HDL concentration and phenotypic distribution of paraoxonase may not be the only determining factors, but that other as yet undetermined factors could be involved in the enzyme activity changes.

The paraoxonase PON1 promoter polymorphism C(-107)T is associated with increased serum glucose concentrations in non-diabetic patients

“…Studies indicate an association between PON1 polymorphisms and various diabetic complications, notably coronary disease (which seems to be more frequent in diabetic [42±47] than in non-diabetic populations [48±54]) as well as retinopathy [55,56], neuropathy [25] and nephropathy [57,58]. Our study suggests PON1 polymorphisms could reflect, and possibly contribute to abnormal glucose control and hence insulin resistance, a risk factor for these complications.…”

Paraoxonase 1 status in the Thai population

“…However, this association was not confirmed in other studies (Ombres et al 1998;Sanghera et al 1998;Cao et al 1998;Herrmann et al 1996) or in a large meta-analysis (Wheeler et al 2004). In addition, low serum PON1 activity has been reported in several diseases, which are associated with accelerated atherosclerosis, including CHD, diabetes mellitus, hypercholesterolaemia and chronic renal failure (Mackness et al 1991b;Abbott et al 1995;Paragh et al 1998;Ikeda et al 1998;Datoine et al 1998). More recently, the PON1 activity phenotype has been shown to be a better predictor of CHD than that of PON1 genotypes .…”

Paraoxonase enzyme activity and dyslipidemia in chronic kidney disease patients

“…Furthemore, studies in children have reported an increased oxidative stress and decreased antioxidants and serum PON level in CKD (12)(13)(14)(15)(16). Serum PON1 level is associated with hyperlipidemia in patients with renal failure but it seems that serum PON level and HDL concentration are not the only determining factors for development of hyperlipidemia (14)(15)(16)(17). Hemodialysis can lower the acrolein level which is a very reactive aldehyde.…”