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Published on: October 12, 2017
Association of High-Density Lipoprotein Subclasses with Chronic Kidney Disease Progression, Atherosclerosis, and
Eiichiro Kanda1,2, Masumi Ai3, Mitsuyo Okazaki4
1Department of Nephrology, Tokyo Kyosai Hospital, Meguroku, Tokyo, Japan.
Insights
High-density lipoprotein (HDL) subclasses are linked to chronic kidney disease (CKD) progression and atherosclerosis. Specific HDL cholesterol proportions correlate with kidney function decline and arterial stiffness, varying by CKD stage.
Area of Science:
- Nephrology
- Cardiology
- Lipidology
Background:
- Atherosclerosis is a common complication in chronic kidney disease (CKD), driven by dyslipidemia and CKD-mineral and bone disorder.
- High-density lipoproteins (HDLs) have diverse subclasses with altered composition and function in CKD.
- Investigating HDL subclasses is crucial for understanding CKD progression and associated atherosclerosis.
Purpose of the Study:
- To explore the role of lipoprotein subclasses in CKD progression.
- To examine the association between lipoprotein subclasses and atherosclerosis.
- To investigate the relationship between lipoprotein subclasses, Klotho, and fibroblast growth factor 23 (FGF23).
Main Methods:
- Prospective cohort study of 71 CKD patients in Japan.
- Quantification of cholesterol proportion and lipoprotein particle numbers across 20 lipoprotein fractions using high-performance gel permeation chromatography.
- Multivariate regression analysis to identify associations adjusted for baseline characteristics.
Main Results:
- Higher particle numbers in small HDLs were observed in Stage 4 CKD compared to Stage 5 CKD.
- In Stage 4 CKD, cholesterol proportions in very small HDLs correlated with estimated glomerular filtration rate (eGFR) change rate and ankle-brachial index (ABI).
- In Stage 5 CKD, serum soluble α-Klotho levels were associated with lipoprotein particle numbers in very small HDLs.
Conclusions:
- HDL subclasses are significantly associated with CKD progression.
- Specific HDL subclasses correlate with atherosclerosis markers like ABI.
- The relationship between HDL subclasses, CKD progression, and Klotho levels is stage-specific in CKD patients.
Background:
Atherosclerosis is often a complication of chronic kidney disease (CKD) because of dyslipidemia and CKD-mineral and bone disorder. High-density lipoproteins (HDLs) are grouped into various subclasses composed of multiple proteins and lipids, and their transformation is altered in CKD. We investigated the roles of lipoprotein subclasses in CKD progression, and atherosclerosis, and the relationships with Klotho and fibroblast growth factor (FGF) 23.
Methods:
Seventy-one CKD patients were enrolled in this prospective cohort study in Japan. The proportions of cholesterol level to total cholesterol level (cholesterol proportion) and lipoprotein particle numbers in 20 lipoprotein fractions were measured by a newly developed high-performance gel permeation chromatography.
Results:
Diabetic nephropathy was observed in 23.9% of the patients. The mean age was 75.0 years and estimated glomerular filtration rate (eGFR) was 17.2 ml/min./1.73m2. The lipoprotein particle numbers in small HDLs were higher in Stage 4 group than in Stage 5 group (p = 0.002). Multivariate regression analysis adjusted for baseline characteristics showed that the cholesterol proportions in very small HDLs were associated with eGFR change rate [F19 β = -17.63, p = 0.036] and ABI [F19 β = 0.047, p = 0.047] in Stage 4 group, and that serum soluble α-Klotho level was associated with the lipoprotein particle numbers in very small HDLs [F19 β = 0.00026, p = 0.012; F20 β = 0.00041, p = 0.036] in Stage 5 group.
Conclusions:
This study showed that HDL subclasses are associated with CKD progression, ABI, and Klotho level in CKD-stage-specific manner.
Related Concept Videos
Chronic Kidney Disease I: Introduction
Chronic Kidney Disease II: Clinical Manifestations
Atherosclerosis I: Introduction
Chronic Kidney Disease III: Interprofessional Care
Atherosclerosis III: Management
Coronary Artery Disease II: Pathophysiology

