Changes in the size and electrophoretic mobility of HDL subpopulation particles in chronic kidney disease.

BACKGROUND: High-density lipoprotein (HDL) is a heterogeneous group of particles with anti-atherogenic properties whose metabolism is alterated in chronic kidney disease (CKD). The aim of this study was to evaluate the particle size and mobility of HDL subpopulations in non-dialysis CKD patients. METHODS: The study involved 42 non-dialysis CKD patients (stages 3a-4) and 18 control subjects. HDL was separated by non-denaturing two-dimensional polyacrylamide gradient gel electrophoresis (2D-PAGGE) and eight HDL subpopulations; preß1, preß2a-c, and α1-4 were distinguished. The size and electrophoretic mobility of HDL subpopulation particles were compared between the groups, and a regression analysis was conducted. RESULTS: In CKD patients, the mean sizes of α-HDL and preß2-HDL particles were significantly lower compared to the control group (8.42 ± 0.32 nm vs. 8.64 ± 0.26 nm, p = 0.014; 11.45 ± 0.51 vs. 12.34 ± 0.78 nm, p = 0.003, respectively). The electrophoretic mobility of preß2-HDL relative to α-HDL was significantly higher in CKD patients compared to the control group (Rf 0.65 ± 0.06 vs. 0.53 ± 0.10, p = 0.002). The size and mobility of HDL subpopulations correlated with eGFR values (p < 0.01). These relationships remained statistically significant after adjusting for age, gender, statin treatment, apolipoprotein AI, total cholesterol, and triglyceride levels. DISCUSSION: CKD affects the size and mobility of HDL particles, which can be related to HDL dysfunction. The magnitude of HDL size and mobility changes depended on CKD stage and differed for individual HDL subpopulations, which indicates that some stages of HDL metabolism may be more affected by the presence of chronic kidney disease.

Non-HDL-C/TG ratio indicates significant underestimation of calculated low-density lipoprotein cholesterol (LDL-C) better than TG level: a study on the reliability of mathematical formulas used for LDL-C estimation.

OBJECTIVES: Low-density lipoprotein cholesterol (LDL-C) is the main laboratory parameter used for the management of cardiovascular disease. The aim of this study was to compare measured LDL-C with LDL-C as calculated by the Friedewald, Martin/Hopkins, Vujovic, and Sampson formulas with regard to triglyceride (TG), LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C)/TG ratio. METHODS: The 1,209 calculated LDL-C results were compared with LDL-C measured using ultracentrifugation-precipitation (first study) and direct (second study) methods. The Passing-Bablok regression was applied to compare the methods. The percentage difference between calculated and measured LDL-C (total error) and the number of results exceeding the total error goal of 12% were established. RESULTS: There was good correlation between the measurement and calculation methods (r 0.962-0.985). The median total error ranged from -2.7%/+1.4% (first/second study) for Vujovic formula to -6.7%/-4.3% for Friedewald formula. The numbers of underestimated results exceeding the total error goal of 12% were 67 (Vujovic), 134 (Martin/Hopkins), 157 (Samspon), and 239 (Friedewald). Less than 7% of those results were obtained for samples with TG >4.5 mmol/L. From 57% (Martin/Hopkins) to 81% (Vujovic) of underestimated results were obtained for samples with a non-HDL-C/TG ratio of <2.4. CONCLUSIONS: The Martin/Hopkins, Vujovic and Sampson formulas appear to be more accurate than the Friedewald formula. To minimize the number of significantly underestimated LDL-C results, we propose the implementation of risk categories according to non-HDL-C/TG ratio and suggest that for samples with a non-HDL-C/TG ratio of <1.2, the LDL-C level should not be calculated but measured independently from TG level.

Disorders of Serum Polyunsaturated Fatty Acids in Renal Transplant Patients.

BACKGROUND: Disturbances in polyunsaturated fatty acids (PUFA) could predispose renal transplant (RTx) patients to cardiovascular risk. The purpose of this study was to evaluate serum content of ω-3 and ω-6 PUFA in RTx subjects, in comparison to nontransplanted chronic kidney disease (CKD) patients in predialysis stages and to healthy controls. In the second part of the study, PUFA were analyzed in subcutaneous adipose tissue of CKD subjects at the time of kidney transplantation. METHODS: The first part of the study was conducted in a cohort (n = 134) of 3 groups: patients after renal transplantation (RTx group, n = 24), patients with CKD in stages 2-5, not on dialysis (CKD-ND group, n = 67), and controls without CKD (control group, n = 43). The fatty acids (FA) assessed by gas chromatography-mass spectrometry (GC-MS) were alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA), and arachidonic acid (AA). Diet was assessed by food frequency questionnaire FFQ-6. In the second part of the study, the same FA were evaluated in samples of adipose tissue taken during the kidney transplantation procedure and compared with FA of controls from the adipose tissue collected during hernia surgeries. RESULTS: The first part of the study showed that RTx patients presented significantly lower serum content of all the examined PUFA, in comparison to the CKD-ND group and controls. For instance, EPA in RTx equaled 0.65 ± 0.32%, in CKD-ND 0.82 ± 0.43%, and in controls 1.06 ± 0.68% (P = .005). No significant correlations were found between serum PUFA and diet in RTx patients. The second part of the study revealed no significant difference in the adipose tissue PUFA between CKD patients at the time of kidney transplantation and controls. CONCLUSIONS: RTx patients present with low serum content of potentially beneficial PUFA. This finding does not seem to be solely due to an altered diet. Observed disorders might result from immunosuppressive drugs or other, yet undetermined, causes.

Plasma Levels of Preß1-HDL Are Significantly Elevated in Non-Dialyzed Patients with Advanced Stages of Chronic Kidney Disease.

In chronic kidney disease (CKD), the level of high-density lipoprotein (HDL) decreases markedly, but there is no strong inverse relationship between HDL-cholesterol (HDL-C) and cardiovascular diseases. This indicates that not only the HDL-C level, but also the other quantitative changes in the HDL particles can influence the protective functionality of these particles, and can play a key role in the increase of cardiovascular risk in CKD patients. The aim of the present study was the evaluation of the parameters that may give additional information about the HDL particles in the course of progressing CKD. For this purpose, we analyzed the concentrations of HDL containing apolipoprotein A-I without apolipoprotein A-II (LpA-I), preß1-HDL, and myeloperoxidase (MPO), and the activity of paraoxonase-1 (PON-1) in 68 patients at various stages of CKD. The concentration of HDL cholesterol, MPO, PON-1, and lecithin-cholesterol acyltransferase (LCAT) activity were similar in all of the analyzed stages of CKD. We did not notice significant changes in the LpA-I concentrations in the following stages of CKD (3a CKD stage: 57 ± 19; 3b CKD stage: 54 ± 15; 4 CKD stage: 52 ± 14; p = 0.49). We found, however, that the preß1-HDL concentration and preß1-HDL/LpA-I ratio increased along with the progress of CKD, and were inversely correlated with the estimated glomerular filtration rate (eGFR), even after adjusting for age, gender, triacylglycerols (TAG), HDL cholesterol, and statin therapy (ß = -0.41, p < 0.001; ß = -0.33, p = 0.001, respectively). Our results support the earlier hypothesis that kidney disease leads to the modification of HDL particles, and show that the preß1-HDL concentration is significantly elevated in non-dialyzed patients with advanced stages of CKD.

Apolipoprotein E gene polymorphism and renal function are associated with apolipoprotein E concentration in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) associates with complex lipoprotein disturbances resulting in high cardiovascular risk. Apolipoprotein E (APOE) is a polymorphic protein with three common isoforms (E2; E3; E4) that plays a crucial role in lipoprotein metabolism, including hepatic clearance of chylomicrons and very low-density lipoprotein (VLDL) remnants, and reverse cholesterol transport. It demonstrates anti-atherogenic properties but data concerning the link between polymorphism and level of APOE in CKD patients are inconclusive. The aim of our research was to assess the relationship between APOE gene polymorphism and APOE concentration and its redistribution among lipoproteins along with CKD progression. METHODS: 90 non-dialysed CKD patients were included into the study. Real time PCR was used for APOE genotyping. APOE level was measured in serum and in isolated lipoprotein fractions (VLDL; IDL + HDL; HDL). Kidney function was assessed using eGFR CKD-EPI formula. RESULTS: The population was divided into three APOE genotype subgroups: E2(ε2ε3), E3(ε3ε3) and E4(ε3ε4). The highest APOE level was observed for the E2 subgroup (p < 0.001). APOE concentration positively correlated with eGFR value in the E2 subgroup (r = 0.7, p < 0.001) but inversely in the E3 subgroup (r = - 0.29, p = 0.02).). A lower concentration of APOE in the E2 subgroup was associated with its diminished contents in HDL and IDL + LDL particles. In the E3 subgroup, the higher concentration of APOE was related to the increased number of non-HDL lipoproteins. CONCLUSION: In patients with CKD, APOE genotype as well as renal function are associated with the concentration of APOE and its redistribution among lipoprotein classes.