Understanding the heterogeneity and dysfunction of HDL in chronic kidney disease: insights from recent reviews

Abstract

Chronic kidney disease (CKD) is a complex disease that affects the global population's health, with dyslipidemia being one of its major complications. High density lipoprotein (HDL) is regarded as the "hero" in the bloodstream due to its role in reverse cholesterol transport, which lowers cholesterol levels in the blood and prevents atherosclerosis. However, in the complex internal environment of CKD, even this "hero" may struggle to perform its beneficial functions and could potentially become harmful. This article reviews HDL heterogeneity, HDL subclasses, functional changes in HDL during the progression of CKD, and the application of HDL in CKD treatment. This review aims to deepen understanding of lipid metabolism abnormalities in CKD patients and provide a basis for new therapeutic strategies.

Keywords: Chronic kidney disease; Dyslipidemia; High density lipoproteins; Subclasses.

Fig. 1

Traditional and specific risk factors for cardiovascular disease in patients with chronic kidney disease. (Adapted from “Risk factors for sarcopenia”, by BioRender.com (2024). Retrieved from https://app.biorender.com/biorender-templates)

Fig. 2

Electron microscopy image showing the morphology of HDL. A: HDL particles in normal individuals are uniform in size, spherical, and aggregate into a single-layer structure. B: HDL particles in patients with LCAT gene deficiency are disc-like and arranged in a stacked formation. (These two images are extracted from the study by Trudy Forte et al. [20])

Fig. 3

Schematic diagram of the HDL structure. (Adapted from “Icon Pack - Metabolism”, by BioRender.com (2024). Retrieved from https://app.biorender.com/biorender-templates)

Fig. 4

The Process of HDL-Mediated Reverse Cholesterol Transport. The liver and intestines synthesize lipid-free ApoA-I, which initially acquires cholesterol and phospholipids from macrophages via ABCA1, forming nascent discoidal HDL. Subsequently, LCAT esterifies the cholesterol, rendering it fully hydrophobic and causing its migration to the core of the discoidal HDL, promoting its maturation into spherical HDL. Meanwhile, membrane proteins such as ABCG1 and SR-BI continue to transfer intracellular cholesterol to HDL, further aiding in HDL maturation. HDL2 and HDL3, the two subclasses of HDL, can interconvert. Next, HDL exchanges cholesteryl esters and triglycerides with VLDL and LDL in equimolar proportions. The final step of reverse cholesterol transport involves the selective uptake of cholesteryl esters from HDL particles by the hepatic SR-BI or the clearance of cholesteryl esters from VLDL and LDL via the LDL receptor (LDLR). (Adapted from “Icon Pack - Lipid”, by BioRender.com (2024). Retrieved from https://app.biorender.com/biorender-templates)