Association of High-Density Lipoprotein Subclasses with Chronic Kidney Disease Progression, Atherosclerosis, and Klotho.

Eiichiro Kanda,Mitsuyo Okazaki,Masumi Ai,Masayuki Yoshida,Yoshitaka Maeda,Tatsuo Shimosawa

doi:10.1371/journal.pone.0166459

Eiichiro Kanda, Mitsuyo Okazaki + Show 4 more

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https://doi.org/10.1371/journal.pone.0166459

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Abstract

BackgroundAtherosclerosis 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.MethodsSeventy-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.ResultsDiabetic 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.ConclusionsThis study showed that HDL subclasses are associated with CKD progression, ABI, and Klotho level in CKD-stage-specific manner.

Highlights

Chronic kidney disease (CKD) patients have high risks of cardiovascular disease (CVD) [1, 2]
Multivariate regression analysis adjusted for baseline characteristics showed that the cholesterol proportions in very small High-density lipoproteins (HDLs) were associated with estimated glomerular filtration rate (eGFR) change rate [F19 β = -17.63, p = 0.036] and ankle-brachial index (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
This study showed that HDL subclasses are associated with chronic kidney disease (CKD) progression, ABI, and Klotho level in CKD-stage-specific manner

Summary

Introduction

Chronic kidney disease (CKD) patients have high risks of cardiovascular disease (CVD) [1, 2]. Atherosclerosis is often a complication of CKD because of dyslipidemia and CKD-mineral and bone disorder (CKD-MBD). High levels of chylomicrons (CMs) and very-low-density lipoproteins (VLDLs) are observed [3, 4]. Nascent HDLs extract cholesterol from peripheral tissues, and transform into HDL3 with cholesterol ester storaged in its core. Cholesterol esterified by lecithin cholesterol acyltransferase (LCAT) is stored in the core of HDL3, and transforms HDL3 into HDL2. 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

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Conclusion