Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients

Abstract

Abstract:Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I (apoA-I) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=−0.306, P=0.012), LDL-C (R=−0.283, P=0.020), and non-HDL-C (R=−0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-β-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.

Stabilization of Oxidative Stress 1 Year after Kidney Transplantation: Effect of Calcineurin Immunosuppressives

“…Rather it increased, but not significantly. However, our results are in agreement with a recent study by Kimak et al 21 who also showed a moderate increase in oxLDL and changes in other lipid parameters in transplant patients. Besides modulation of lipid parameters, a decrease in paraoxonase 1 (POX1) activity in CRF patients was observed.…”

“…The mild increase in oxLDL after KT could be associated with incomplete restoration of POX1 activity and HDL function. 21,22 Our results also demonstrated that the level of AOPPs, one of the end products of OS, is a reliable and sensitive marker for estimating the effectiveness of therapy and the degree of OS in patients suffering from chronic kidney disease. Its determination seems to be better than oxLDL levels for monitoring the real situation in the body.…”

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“…13 Kidney transplant recipients have hypertriglyceridemia; hypercholesterolemia; moderately decreased HDL cholesterol, HDL particle concentration, and PON1 activity; and moderately increased oxidized LDL and antioxidized LDL antibody levels compared with controls; however, oxidized LDL and antioxidized LDL antibody levels may be increased and PON1 activity may be decreased in hemodialysis patients. 14 These results show that oxidized LDL and decreased PON1 activity in transplant recipients may cause more mildly oxidized HDL, which may be less stable and which may undergo metabolic remodeling, generate a greater number of smaller pre-β-HDL particles, and accelerate reverse cholesterol transport. This may be beneficial for transplant recipients.…”

“…This may be beneficial for transplant recipients. 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.…”

“…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.…”