Lipid disorders and their relevance to outcomes in chronic kidney disease

Cardiovascular disease is the major cause of death in patients with chronic kidney disease (CKD). Cardiovascular disease and many other complications of CKD are mediated by oxidative stress, inflammation, and dyslipidemia. This review provides a concise overview of the nature and mechanisms of CKD-induced lipid disorders and their adverse consequences. Lipid abnormalities in end-stage renal disease are characterized by: (a) reduced serum apoA-1 and high-density lipoprotein (HDL) concentrations, impaired HDL maturation and defective HDL antioxidant, anti-inflammatory and reverse cholesterol transport properties; (b) impaired clearance of very low-density lipoprotein and chylomicrons by the muscle and adipose tissue and of their remnants by the liver leading to hypertriglyceridemia, accumulation of intermediate-density lipoprotein and chylomicron remnants, and (c) oxidative modification of LDL and lipoprotein remnants favored by their structural abnormalities, oxidative stress, and impaired HDL antioxidant activity. Together these abnormalities result in: (a) uptake of oxidized LDL and remnant particles by macrophages and resident cells in the artery wall which along with impaired HDL-mediated reverse cholesterol transport causes foam cell formation and atherosclerosis, (b) production of inflammatory mediators and reactive oxygen species by leukocytes and macrophages in response to stimulation by oxidized LDL and phospholipids leading to intensification of oxidative stress and inflammation, (c) dissemination of oxidative stress by circulating oxidized lipids and lipoproteins via lipid peroxidation chain reaction, (d) heightened injurious effects of oxidative stress and inflammation due to diminished antioxidant, anti-inflammatory and antithrombotic activities of HDL, and finally (e) impaired ability of very low-density lipoprotein and chylomicron to deliver lipid fuel to muscle and adipose tissue contributing to muscle weakness and cachexia which commonly occur in end-stage renal disease patients.