Plasma Levels of Preβ1-HDL Are Significantly Elevated in Non-Dialyzed Patients with Advanced Stages of Chronic Kidney Disease

Abstract

In chronic kidney disease (CKD), the level of high-density lipoprotein (HDL) decreases markedly, but there is no strong inverse relationship between HDL-cholesterol (HDL-C) and cardiovascular diseases. This indicates that not only the HDL-C level, but also the other quantitative changes in the HDL particles can influence the protective functionality of these particles, and can play a key role in the increase of cardiovascular risk in CKD patients. The aim of the present study was the evaluation of the parameters that may give additional information about the HDL particles in the course of progressing CKD. For this purpose, we analyzed the concentrations of HDL containing apolipoprotein A-I without apolipoprotein A-II (LpA-I), preβ1-HDL, and myeloperoxidase (MPO), and the activity of paraoxonase-1 (PON-1) in 68 patients at various stages of CKD. The concentration of HDL cholesterol, MPO, PON-1, and lecithin-cholesterol acyltransferase (LCAT) activity were similar in all of the analyzed stages of CKD. We did not notice significant changes in the LpA-I concentrations in the following stages of CKD (3a CKD stage: 57 ± 19; 3b CKD stage: 54 ± 15; 4 CKD stage: 52 ± 14; p = 0.49). We found, however, that the preβ1-HDL concentration and preβ1-HDL/LpA-I ratio increased along with the progress of CKD, and were inversely correlated with the estimated glomerular filtration rate (eGFR), even after adjusting for age, gender, triacylglycerols (TAG), HDL cholesterol, and statin therapy (β = −0.41, p < 0.001; β = −0.33, p = 0.001, respectively). Our results support the earlier hypothesis that kidney disease leads to the modification of HDL particles, and show that the preβ1-HDL concentration is significantly elevated in non-dialyzed patients with advanced stages of CKD.

Paraoxonase 1 and atherosclerosis‐related diseases

“…In particular, we found that HDL distribution was shifted toward smaller HDL 3 particles in both patient groups, because of impaired HDL maturation, due to reduced apoA‐I level and LCAT activity. Our findings were further extended in a recent study in nondialysis CRD patients by Kuchta and colleagues . They found that the level of preβ1‐HDL, the smallest HDL particles in plasma, increased in advanced stages of CRD .…”

“…Our findings were further extended in a recent study in nondialysis CRD patients by Kuchta and colleagues . They found that the level of preβ1‐HDL, the smallest HDL particles in plasma, increased in advanced stages of CRD . Preβ1‐HDL particles are considered as initial acceptors of cholesterol in the first step of the RCT process .…”

“…However, their level is increased in patients with CVD and CRD, indicating altered HDL maturation, increased production, or delayed catabolism of small HDL particles, which is particularly relevant in CRD . In our study, PON1 activity gradually decreased with progression of CRD toward ESRD, while Kuchta and colleagues further demonstrated that patients with stages 3 and 4 CRD had similar PON1 activities. Although we found that PON1 was more abundant on HDL 3 subclasses in CRD and ESRD patients, PON1 activity in HDL 3 particles was significantly lower than in controls .…”

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

“…Elevated concentrations of preβ1-HDL have been also observed in patients with coronary artery disease, which suggests the relationship between higher levels of preβ1-HDL and the risk of CVD [126,127]. Kuchta et al [125] reported a substantial increase of preβ1-HDL in patients with 3a-4 stages of CKD, which was probably associated with a compromised LCAT-dependent conversion of preβ1-HDL into α-migrating HDL. Other studies have confirmed that CKD decreased both levels and activity of circulating LCAT, and in advanced stages of the disease, it downregulated hepatic LCAT gene expression [128,129].…”

“…Therefore, low levels of large HDL particles and high levels of small HDL particles seem to protect against the incidence of cardiovascular events [16,124]. Kuchta et al [125] demonstrated that, in CKD patients with stages 3a-4, the concentration of preβ1-HDL was increased. Elevated concentrations of preβ1-HDL have been also observed in patients with coronary artery disease, which suggests the relationship between higher levels of preβ1-HDL and the risk of CVD [126,127].…”