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

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.