Lipoproteins in chronic kidney disease: from bench to bedside

Area of Science:

• Nephrology
• Cardiology
• Lipid Metabolism

Background:

• Chronic kidney disease (CKD) significantly elevates cardiovascular disease (CVD) risk.
• CKD patients present with 'uraemic dyslipidaemia', a distinct lipid profile characterized by normal LDL cholesterol, low HDL cholesterol, and high triglycerides.
• All major lipoprotein classes contribute to the pathogenesis of CKD-associated CVDs.

Purpose of the Study:

• To elucidate the role of altered lipoproteins in CKD-associated cardiovascular complications.
• To understand the structural and functional modifications of lipoproteins in uraemia.
• To highlight the need for novel therapeutic strategies targeting lipoprotein remodelling in CKD.

Main Methods:

• Analysis of lipoprotein structure and function in CKD patients.
• Investigation of uraemia-induced modifications including proteomic and lipidomic changes.
• Assessment of the impact of modified lipoproteins on cellular processes involved in atherogenesis.

Main Results:

• Uraemia induces significant structural changes in lipoproteins, affecting their proteome, lipidome, and accumulating small molecules.
• Modified lipoproteins from CKD patients exhibit impaired lipid transport and promote inflammation, oxidative stress, and endothelial dysfunction.
• These alterations in lipoprotein functionality contribute directly to atherogenesis and CKD-associated CVD development.

Conclusions:

• Uraemic dyslipidaemia is a key driver of cardiovascular risk in CKD.
• Current lipid-modifying therapies have limited efficacy due to kidney function modulation.
• Development of novel agents targeting lipoprotein remodelling and function is crucial for managing CVD in CKD patients.