Abstract

Chronic kidney disease (CKD) is a worldwide concern with a high economic cost to health systems due to its high prevalence. It is currently estimated that 10% to 15% of the general population has CKD. It shows an increasing incidence largely driven by an aging population and the growing prevalence of diabetes, hypertension and obesity. CKD shows a high cardiovascular morbidity and premature mortality. Atherosclerosis is closely related to lipid abnormalities. In fact, the European Society of Atherosclerosis recently stated that low-density lipoprotein cholesterol (LDL-C) directly cause atherosclerotic cardiovascular disease. Traditional lipid parameters do not explain the excess and the rapid progression of atherosclerosis present in the CKD population. Lipoprotein classes consist of a wide spectrum of particles of different size and density, and their relevant changes cannot be detected by traditional lipid parameters. In that sense, advanced lipoprotein tests (ALT) that allow a detailed characterization of lipoprotein particles have been proposed as important tools for cardiovascular risk assessment. The present study combines traditional lipid parameters obtained in the daily clinical practice with an ALT performed by NMR. The aims of the study were to assess the association between GFR and lipid parameters, and evaluate their discrimination ability in non-diabetic CKD patients without statin therapy. Cross-sectional study of a subcohort including 209 CKD patients at various stages of the disease belonging to the NEFRONA study. Patients with diabetes and/or on statin therapy were excluded from the present study. The study sample included 86 patients with GFR 30-59 mL/min/1.73 m2 (CKD stage 3), 71 GFR <30 (CKD stage 4-5) and 52 in dialysis, besides, 186 controls. The traditional lipid profile revealed that the levels of total cholesterol (TC), and the cholesterol content in HDL, LDL and non-HDL lipoproteins (referred as HDL-C, LDL-C and non-HDL-C, respectively, decreased as GFR declined, although they were slightly lower in the highest GFR group (>90 ml/min/1.73m2) than in the GFR 60-89 ml/min/1.73m2 group. On the contrary, the levels of triglycerides (TG) and Lp(a) rose as GFR decreased. The ratio TG/HDL-C increased as GFR declined indicating an accumulation of TG and a reduction of HDL-C when GFR was compromised. By NMR: LDL lipoproteins showed a reduction of cholesterol (referred as LDLr-C) and gained triglycerides (referred as LDL-TG) as GFR was compromised. As GFR declined, the ratio LDLr-C/total LDL particle was reduced indicating that although cholesterol content of LDL particles decreased, there were more circulating LDL particles. There was a reduction of the average LDL size as GFR was declined due to an accumulation of small particles (high ratio small/total LDL particles) and a reduction of large particles (low ratio large/total LDL particles). Our major finding is that this study revealed many pro-atherogenic lipoprotein abnormalities associated with GFR reduction, such as an accumulation of VLDL particles, an increase of lipid content in VLDL, and a reduction of LDL average particle size. Interestingly, some NMR-assessed parameters showed a higher discrimination capacity than traditional parameters.

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