Serum Paraoxonase Activity Changes in Uremic and Kidney-Transplanted Patients

Abstract

Serum paraoxonase (PON) is a high-density lipoprotein (HDL)-associated hydrolase, which inhibits low-density lipoprotein oxidation. Uremic and kidney-transplanted patients have an increased risk of atherosclerosis, to which an increased lipoprotein oxidation may contribute. The aim of our study was to determine whether the PON activity or phenotype is altered in uremic and kidney-transplanted patients, and to compare the values with those of healthy controls. 117 uremic patients on long-term hemodialysis treatment, 115 renal-transplanted patients, and 110 healthy controls were involved in the study. The PON activity was significantly reduced in the uremic patients compared to controls (PON 101.36±30.12 vs. control 188.05±58.96 U/ml; p < 0.001), while in kidney-transplanted patients the values were almost identical to those of controls (PON 161.5±35.39 U/ml). The different immunosuppressive drug combinations did not influence PON activity. To assess whether the altered PON activity was due to a decrease HDL level, we standardized the enzyme activity for the HDL concentration (PON/HDL ratio). We found that the standardized enzyme activity was lower in the uremic (102.7±54.8) and kidney-transplanted patients (144.5±32.7) when compared to controls (194.5±94.5; p < 0.001). The phenotypic distribution of PON in uremic, renal transplant and control patients are as follows: AA 66.67, 56.48 and 66.67%; AB 31.62, 33.3 and 26.67%; BB 1.71, 10.19 and 6.67%. We conclude that the decreased PON/HDL and PON/apoA-1 ratios may lead to a reduction in the antioxidant capacity of HDL, which might contribute to the accelerated development of atherosclerosis in uremic and kidney-transplanted patients.

Serum Cystatin C Is a Determinant of Paraoxonase Activity in Hemodialyzed and Renal Transplanted Patients

“…Previous studies have indicated that PON1 can prevent low density lipoprotein (LDL) oxidation by hydrolyzing lipid peroxides in lipoproteins, deoxify homocysteine thiolactone and therefore protect against the development of atherosclerosis [2][3][4]. The enzyme's activity is reduced in patients with enhanced atherosclerosis, in disorders of lipoprotein metabolism, in renal insufficiency and after renal transplantation, caused by elevated oxidative stress and disturbances of apolipoprotein metabolism [5]. PON1 has newly been discovered to possess lactonase activity, and hydrolyze various lactones, thiolactones and cyclic carbonate esters.…”

Hyperleptinemia Is Not Responsible for Decreased Paraoxonase Activity in Hemodialysis Patients

“…Previously, we [4] and others [5] demonstrated decreased PON1 activity in HD patients, and kidney transplantation can partially reverse it [6]. Cardiovascular diseases and accelerated atherosclerosis are known complications in HD patients, and the enhanced oxidative stress [7, 8] is concomitant with the decreased antioxidant defense system [4, 5] measured also by α-tocopherol levels [9].…”

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“…14 Another study concluded that immunosuppressive drug combinations do not affect PON activity. 15 After a kidney transplant, continuous immunosuppressive therapy (cyclosporine, azathioprine, and methylprednisolone) produced other predisposing factors for accelerating atherosclerosis. 15 Arterial stiffness may be a marker for the development of future atherosclerotic disease or may be more directly involved in the process of atherosclerosis in uremic and nonuremic patients.…”

“…3,[10][11][12] Low PON1 levels in uremic patients have been restored after kidney transplant. 5,[13][14][15] However, there are few studies that compare the effect of calcineurin inhibitors on oxidant and an antioxidant system indices in kidney transplant recipients. [16][17][18][19][20] The purpose of this prospective study was to evaluate the effects of the calcineurin inhibitors tacrolimus and cyclosporine on cardiovascular disease risk factors, including high-sensitivity CRP (hsCRP), homocysteine, malondialdehyde (MDA, a lipid peroxidation biomarker of oxidative stress), and activity of PON and arylesterase (components of the antioxidant system), in kidney transplant recipients.…”