Dyslipidemia in chronic kidney disease

Abstract

Lipid abnormalities in chronic kidney disease (CKD) attract continuous attention due to their unclear involvement in CKD patient outcome and controversial management. If kidney function declines, inflammation and oxidative stress progress and lipid disturbances develop. Malnutrition may ameliorate dyslipidemia in advanced CKD. CKD-related dyslipidemia is characterized by high-density lipoprotein (HDL) cholesterol deficiency, HDL dysfunction, and hypertriglyceridemia. Additionally, an accumulation of very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), apolipoprotein (Apo) B, lipoprotein (a) particles, and increased ApoCIII/ C-II ratio are detected. Total plasma levels of low-density lipoprotein cholesterol (LDL) may be normal or increased, but small-density fraction of LDL and oxidized LDL increase. The acyl-CoA cholesterol acyltransferase is upregulated. As a lecithin-cholesterol acyl-transferase deficiency occurs in CKD, HDL-3 maturation into HDL-2 is diminished. Lipidomics studies in CKD indicate increased levels of free fatty acids, glycerolipid, and glycerophospholipids. There is a negative association between estimated glomerular filtration rate and methyl hexadecanoic acid and 3-oxooctadecanoic acid. In CKD patients requiring hemodialysis (HD), palmitic acid and monounsaturated fatty acid levels are increased, whereas polyunsaturated fatty acid levels are decreased. In advanced CKD, a pattern of dyslipidemia depends on dialysis modality (HD, peritoneal dialysis). Nephrotic syndrome, if it occurs in the course of CKD, is characterized by increased cholesterol, TG, and ApoB containing lipoproteins (including VLDL, IDL, and lipoprotein (a)), whereas HDL, ApoA1, and ApoA2 levels are normal or close to normal values. The ratio of HDL cholesterol to total serum cholesterol is substantially decreased. The severity of dyslipidemia in nephrotic syndrome correlates with the magnitude of proteinuria. CKD-related dyslipidemia, together with other traditional (older age, male gender, smoking, hypertension, diabetes, impaired energy metabolism) and nontraditional (uremic toxins, inflammation, oxidative stress, endothelial dysfunction, anemia, mineral and bone disorders, disturbed thyroid function) cardiovascular disease (CVD) risk factors, accelerates formation of atherosclerotic plaques and contributes to development of CVDs, including coronary artery disease, and cerebral ischemia. CVDs are the main cause of morbidity and mortality of CKD patients, but studies on direct associations of dyslipidemia with mortality yield controversial results. Guidelines for dyslipidemia management in CKD were elaborated by the Kidney Disease: Improving Global Outcomes organization. They include health behavior modification that is indicated in all CKD subjects and pharmacological treatment that should be recommended in the predialysis CKD stages and continued during dialysis as needed.