Mechanisms for increased cardiovascular disease in chronic kidney dysfunction.

PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) have the highest risk for atherosclerotic cardiovascular disease (CVD). Current interventions have been insufficiently effective in lessening excess incidence and mortality from CVD in patients with CKD versus other high-risk groups. This review focuses on traditional and CKD-related risks as well as key mechanisms of macrophage foam cell formation that underlie the excess CVD in the setting of CKD.

RECENT FINDINGS: Hyperlipidemia, particularly increased low-density lipoprotein (LDL) cholesterol, is the key factor in atherogenesis in the general population, but has not been found to be the overriding risk for greater CVD in CKD, especially as renal damage progresses. Although higher incidence of CVD in CKD is not due to higher serum lipids per se, CKD is associated with abnormal lipid metabolism that is proatherogenic. CKD-related risks, including inflammation and disturbances in mineral metabolism, have been implicated. In addition, perturbations of the macrophage, a cell that is central in atherogenesis, may be important.

SUMMARY: The mechanisms underlying the heightened risk for CVD in CKD have been the focus of intense study and may relate to the combined effects of traditional and CKD-specific risks involving inflammation and lipid metabolism, especially perturbation of macrophage cholesterol homeostasis.