Carbamylated low-density lipoprotein: nontraditional risk factor for cardiovascular events in patients with chronic kidney disease

Abstract

The high cardiovascular morbidity and mortality associated with chronic kidney disease (CKD) cannot be explained entirely by traditional risk factors. Urea spontaneously dissociates to form cyanate, which modifies proteins in a process referred to as carbamylation. Carbamylated low-density lipoprotein (cLDL) has been shown to have all of the major biological effects relevant to atherosclerosis, including endothelial cell injury, increased expression of cell adhesion molecules, and vascular smooth muscle cell proliferation. Recent studies indicate that cLDL leads to endonuclease G activation, which participates in cellular injury. In addition, cLDL has been shown to enhance generation of oxidants. Limited human data have demonstrated high levels of cLDL in hemodialysis patients, with the highest levels in patients who have atherosclerosis. In 2 separate clinical studies, plasma levels of carbamylated protein independently predicted an increased risk of coronary artery disease, future myocardial infarction, stroke, and death. Future prospective studies to examine the association and/or predictive value of cLDL and studies to establish cause-effect relationship in patients with CKD are needed.