Cholesterol Metabolism in CKD.
Patients with chronic kidney disease (CKD) have a substantial risk of developing coronary artery disease. Traditional cardiovascular disease (CVD) risk factors such as hypertension and hyperlipidemia do not adequately explain the high prevalence of CVD in CKD. Both CVD and CKD are inflammatory states and inflammation adversely affects lipid balance. Dyslipidemia in CKD is characterized by elevated triglyceride levels and high-density lipoprotein levels that are both decreased and dysfunctional. This dysfunctional high-density lipoprotein becomes proinflammatory and loses its atheroprotective ability to promote cholesterol efflux from cells, including lipid-overloaded macrophages in the arterial wall. Elevated triglyceride levels result primarily from defective clearance. The weak association between low-density lipoprotein cholesterol level and coronary risk in CKD has led to controversy over the usefulness of statin therapy. This review examines disrupted cholesterol transport in CKD, presenting both clinical and preclinical evidence of the effect of the uremic environment on vascular lipid accumulation. Preventative and treatment strategies are explored.
Department of Medicine and Winthrop Research Institute, Winthrop University Hospital, Mineola, NY. Electronic address: areiss@winthrop.org.
Allison B
AB
Reiss
Department of Medicine and Winthrop Research Institute, Winthrop University Hospital, Mineola, NY.
Iryna
I
Voloshyna
Department of Medicine and Winthrop Research Institute, Winthrop University Hospital, Mineola, NY.
Joshua
J
De Leon
Department of Medicine and Winthrop Research Institute, Winthrop University Hospital, Mineola, NY.
Nobuyuki
N
Miyawaki
Department of Medicine and Winthrop Research Institute, Winthrop University Hospital, Mineola, NY.
Joseph
J
Mattana
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D006801:Humans; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D012307:Risk Factors
D008076:Cholesterol, HDL
Cholesterol transport; atherosclerosis; cardiovascular disease (CVD); chronic kidney disease (CKD); dyslipidemia; high-density lipoprotein (HDL); inflammation; lipid-lowering therapy; low-density lipoprotein (LDL); nontraditional risk factor; reactive oxygen species (ROS); statin therapy; uremic toxins