Lipid metabolism abnormalities in Chronic Kidney Disease

Abstract

Regardless of the etiology of renal disease, patients with chronic kidney disease (CKD) develop profound qualitative and quantitative lipoprotein metabolism abnormalities because of the presence of alterations in apolipoproteins, lipid transfer proteins, lipolytic enzymes, and lipoprotein receptors from the earlier stages of the disease. As renal function deteriorates, triglyceride concentrations increase and high-density lipoprotein cholesterol (HDL) concentrations decline, while levels of low- density lipoprotein (LDL) cholesterol remain in the normal range or become slightly decreased. Meanwhile, there is a progressive accumulation of the more atherogenic small dense LDL particles. In stages 4 and 5 of CKD, there is decreased concentration of apolipoprotein A-containing lipoproteins, and increased concentrations of triglyceride-rich apolipoprotein B-containing lipoproteins. Patients with nephrotic syndrome and preserved glomerular filtration rate show a higher atherogenic profile, with markedly elevated plasma cholesterol, triglyceride concentrations, and increased very low (VLDL) and low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and lipoprotein(a) levels. Depressed plasma HDL cholesterol concentrations are also commonly observed in patients with nephrotic syndrome.

Unless nephrotic syndrome is present, lipid abnormalities are not commonly observed when the lipid profile is measured using standard quantitative methods. In particular, total and LDL cholesterol, the most common lipid parameters used to stratify the cardiovascular risk and assess the effect of treatment with statins, are usually normal and often low. However, there is evidence that some alterations of the qualitative profile of lipoprotein are characteristic of chronic kidney disease, and probably contribute to the high rate of atherosclerotic events observed in these patients. These qualitative abnormalities include increased levels of VLDL and IDL cholesterol, small dense and oxidized LDL particles and lipoprotein(a). Moreover, HDL cholesterol is usually low and dysfunctional, not acting as protective, but paradoxically as proatherogenic particles.

The lipid profile of CKD shows similar features to the metabolic syndrome and type 2 diabetes, conditions well known to predispose to kidney disease, which in turn aggravates insulin resistance and promotes atherogenic dyslipidemia.