Lipid Disorders and Their Relevance to Outcomes in Chronic Kidney Disease

Abstract

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.

Relation of Serum Lipids and Lipoproteins with Progression of CKD

“…Dyslipidemia is common in patients with CKD and is characterized by elevated plasma triglyceride and VLDL-C levels and diminished plasma HDL-C concentrations (25). This pattern in the lipid profile was also seen at baseline in CRIC study participants (26).…”

Mid-Adulthood Risk Factor Profiles for CKD

“…26 The accumulation of both triglycerides and the breakdown products of lipid metabolism in the blood of patients with CKD also has potent atherogenic and proinflammatory effects on the vasculature in the kidney and beyond the renal parenchyma. 27 The presence of elevated CKD risk factors in mid-adulthood illustrates the importance of time in the assessment of risk factor exposure. Both the duration of exposure and the particular time of life at which one is exposed to a particular risk factor may play a role in future CKD.…”

Role of dyslipidemia in impairment of energy metabolism, oxidative stress, inflammation and cardiovascular disease in chronic kidney disease

“…In addition to causing hypertriglyceridemia, impaired clearance of triglyceride-rich lipoproteins contributes to cachexia, malnutrition, reduced exercise capacity, and altered energy metabolism in CKD patients [1]. In this context the CKD-induced LPL and VLDL receptor deficiencies limit the supplies of lipid fuel and construction material to the skeletal muscles, myocardium and adipose tissues [32].…”

“…Advanced chronic kidney disease (CKD) results in a triad of oxidative stress, inflammation and dyslipidemia which form a vicious circuit that promotes progression of kidney disease, cachexia, diminished exercise capacity, cardiovascular disease, and numerous other complications [1]. Patients with end-stage renal disease (ESRD) maintained on hemodialysis have elevated serum triglyceride, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), chylomicron remnants, and oxidized lipoproteins.…”