Subpopulations of High-Density Lipoprotein: Friends or Foes in Cardiovascular Disease Risk in Chronic Kidney Disease?

Abstract

Dyslipidemia is a major traditional risk factor for cardiovascular disease (CVD) in chronic kidney disease (CKD) patients, although the altered lipid profile does not explain the number and severity of CVD events. High-density lipoprotein (HDL) is a heterogeneous (size, composition, and functionality) population of particles with different atherogenic or atheroprotective properties. HDL-cholesterol concentrations per se may not entirely reflect a beneficial or a risk profile for CVD. Large HDL in CKD patients may have a unique proteome and lipid composition, impairing their cholesterol efflux capacity. This lack of HDL functionality may contribute to the paradoxical coexistence of increased large HDL and enhanced risk for CVD events. Moreover, CKD is associated with inflammation, oxidative stress, diabetes, and/or hypertension that are able to interfere with the anti-inflammatory, antioxidative, and antithrombotic properties of HDL subpopulations. How these changes interfere with HDL functions in CKD is still poorly understood. Further studies are warranted to fully clarify if different HDL subpopulations present different functionalities and/or atheroprotective effects. To achieve this goal, the standardization of techniques would be valuable.

Keywords: HDL functionality; HDL subpopulations; cardiovascular disease risk; chronic kidney disease; inflammation; oxidative stress.

Figure 1

Illustration of high-density lipoprotein (HDL) separation into subfractions of one studied control (a) and one end-stage renal disease patient on dialysis (b) using the Lipoprint® kit from Quantimetrix Corp. (Redondo Beach, CA, USA). (HDL is separated into 10 subfractions that are classified as large HDL (1–3 subfractions—green color), intermediate HDL (4–7 subfractions—yellow color), and small HDL (8–10 subfractions—red color)).

Figure 2

Schematic view of the major alterations in HDL composition in chronic kidney disease. (Apo, apolipoprotein; AMBP, α-1-microglobulin/bikunin precursor; β2M, β-2-microglobulin; CETP, cholesteryl ester transfer protein; GPx, glutathione peroxidase; LCAT, lecithin–cholesterol acyltransferase; PON1, paraoxonase 1; RBP, retinol binding protein; SAA, serum amyloid; SP-B, surfactant protein B; ↑, increases; ↓, decreases).