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Characteristics of Lipid Metabolism Including Serum Apolipoprotein M Levels in Patients with Primary Nephrotic Syndrome

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Characteristics of Lipid Metabolism Including Serum Apolipoprotein M Levels in Patients with Primary Nephrotic Syndrome He et al. Lipids in Health and Disease (2017) 16:167 DOI 10.1186/s12944-017-0556-9 RESEARCH Open Access Characteristics of lipid metabolism including serum apolipoprotein M levels in patients with primary nephrotic syndrome Lagu He1, Pengfei Wu2, Li Tan1, Bai Le1, Wenhan Du1, Ting Shen1, Jiali Wu1, Zheyi Xiang1 and Min Hu1* Abstract Background: Apolipoprotein M (apoM) is a 26-kD apolipoprotein that is mainly expressed in specific cell types, such as human liver parenchymal cells and kidney proximal renal tubular epithelial cells. ApoM can regulate the formation of pre-β-HDL and the reverse cholesterol transport and thus plays an important role in the metabolism of lipids and lipoproteins, meaning that it can affect the development of lipid metabolism disorders. Significantly elevated serum apoM levels are detected in patients with hyperlipidemia. However, few studies have shown how apoM is expressed in primary nephrotic syndrome (PNS), which is often accompanied with hyperlipidemia, and the underlying mechanism is poorly understood. This study was aimed at examining the apoM levels in patients with PNS and at determining the effects of PNS on serum apoM levels in these patients. Methods: This study included patients with hyperlipidemia (n = 37), the PNS with hyperlipidemia group (n = 62), PNS without hyperlipidemia group (n = 33), and healthy controls (n = 73). The age and body–mass index (BMI) matched among the groups of participants. Their serum apoM concentrations were measured by an enzyme-linked immunosorbent assay. Serum levels of conventional lipids and renal function indices were assessed using an automatic biochemical analyzer. The data were analyzed by means of Pearson’s correlation coefficient (continuous variables) or Student’s t test (mean differences). Results: The average serum apoM concentrations were higher in the hyperlipidemia group (61.1 ± 23.2 mg/L, P = 0.004) than in the healthy controls (31.6 ± 18.92 mg/L). The serum apoM concentrations were lower in the PNS with hyperlipidemia group (25.1 ± 16.31 mg/L, P = 0.007) and in the PNS without hyperlipidemia group (21.00 ± 17. 62 mg/L, P = 0.003) than in the healthy controls. The serum apoM concentrations in the PNS with hyperlipidemia group did not differ significantly from those in the PNS without hyperlipidemia group (P = 0.083). Moreover, serum apoM levels positively correlated with serum high-density lipoprotein cholesterol (HDL-C) and apoA1 levels and negatively correlated with proteinuria in PNS patients (r = 0.458, P =0.003;r = 0.254, P = 0.022; r = −0.414, P = 0.028). Conclusion: Serum apoM concentrations are higher in patients with hyperlipidemia than in healthy controls. Low serum apoM levels in patients with PNS are likely caused by PNS. Keywords: Apolipoprotein M,PNS, HDL, Lipids, Hyperlipidaemia * Correspondence: [email protected] 1Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. He et al. Lipids in Health and Disease (2017) 16:167 Page 2 of 9 Background China) between July 2016 and June 2017. The diagnosis Primary nephrotic syndrome (PNS) is a common pro- of PNS was based on each patient’s clinical history, gressive kidney disease occurring in childhood and char- physical examinations according to the Global Initia- acterized by a selective change in the glomerular tive. The diagnostic criteria were (1) proteinuria capillary wall; this change prevents the wall from limit- >50 mg/(kg⋅d), (2) plasma albumin < 25 g /l, (3) ing the loss of protein with urine [1]. Nephrotic edema, (4) HLP. (1),(2) are necessary. Hyperlipidemia syndrome is characterized by substantial proteinuria, was defined according to the Adult Treatment Panel hypoproteinemia, edema, and hyperlipidemia (HLP), and III of the National Cholesterol Education Program a group of symptoms featured in metabolic syndrome. (serum total [TGs] ≥ 220 mg/dL [2.49 mmol/L] or Hyperlipidemia is often accompanied with complex dys- serum total cholesterol [THOL] ≥ 240 mg/dL lipidemia, such as elevated very low-density lipoprotein [6.24 mmol/L]) [11]. The exclusion criteria were (1) cholesterol (VLDL-C) and LDL-C levels and low high- diabetes, (2) pregnancy, (3) thyroid disease, (4) cancer, density lipoprotein cholesterol (HDL-C) levels, which (5) immunological disease, (6) congestive heart failure, are associated with serum apolipoprotein M (apoM) [2]. (7) another renal disease, (8) metabolic acidosis, or ApoM is a 26-kD apolipoprotein that belongs to the (9) venous or arterial thrombosis. Hyperlipidemia lipocalin protein family [3]. ApoM is mainly expressed patients who used lipid-lowering drugs and PNS in specific cell types, such as human liver parenchymal patients who received steroid therapy were also cells and kidney proximal renal tubular epithelial cells excluded. The control group included 73 nonallergic [4]. Studies have revealed that apoM can regulate the volunteers without renal disease and 37 hyperlipid- formation of pre-β-HDL and the reverse cholesterol emia controls without other diseases who underwent transport, thus playing an important role in the metabol- physical examination in our hospital. The main clin- ism of lipids and lipoproteins, indicating that it can ical and biochemical characteristics of the four groups affect the development of lipid metabolic disorders, such in this study are shown in Table 1. as coronary artery disease, nephrotic syndrome, and liver disease [5]. The mechanism of nephritic HLP is compli- Blood sampling cated. The prevailing view is that the liver synthesis of After an overnight fast and at least 20 min of rest, blood lipids and apolipoproteins is increased, and the clearance samples were collected from each subject. Serum was rates of chylomicrons and VLDL are reduced [6]. Hyper- obtained by centrifugation at 3500 rpm for 5 min, and lipidemic mice with defective LDL receptor have a high aliquots were stored at −80°C. plasma level of triglycerides (TGs) and serum apoM [7]. Therefore, we hypothesized that the level of apoM may ELISA for apoM quantification be associated with hyperlipidemia. Researchers have Serum apoM levels were measured by a sandwich ELISA found that there are different characteristics of lipid me- (Yuan Tai Bio Inc., Changsha, Hunan, The People’s tabolism at different levels of urinary protein excretion vhRepublic of China). Optical density (OD) was mea- (UPE) [8]. HLP, the main complication of PNS, is sured at 450 nm (with a background reading at 620 nm), thought to be involved in cardiovascular disease (CVD) using an ELX-800 absorbance reader (BioTek Instru- and in progressive glomerular damage leading to renal ments, Inc., Winooski, VT, USA). The concentration of failure [9, 10]. ApoM is mainly expressed in human liver apoM (in mg/L) in each sample was determined using a parenchymal cells and kidney proximal renal tubular standard curve. epithelial cells. Therefore, the specific effect of hyperlip- idemia on serum apoM in patients with PNS should be Assays of lipoproteins and renal-function indices studied to confirm whether the concentration of apoM Levels of serum TGs, THOL, HDL cholesterol (HDL-C), is associated with hyperlipidemia or PNS. The aim of LDL cholesterol (LDL-C), apolipoprotein A1 (apoA1), this study was to measure the apoM levels in patients apolipoprotein B (apoB), lipoprotein a (Lpa), Nrinary with hyperlipidemia, patients with PNS and hyperlipid- neutrophil gelatinase-associated lipocalin (NGAL), and emia, and patients with PNS but without hyperlipidemia other renal injury biomarkers (cystatin-C [CysC], cre- by an enzyme-linked immunosorbent assay (ELISA). atinine [CRE], blood urea nitrogen [BUN], and uric acid This study was also aimed at determining the effects of [UA]) were measured on an ARCHITECT c8000 System serum apoM in patients with PNS. (Abbott Laboratories, Irving, TX, USA). Methods Statistical analysis Subjects Continuous variables are presented as mean ± standard This was a case-control study of PNS patients conducted deviation. Relations between continuous variables were at the Second Xiangya Hospital (Changsha, Hunan, tested by means of Pearson’s correlation coefficient. He et al. Lipids in Health and Disease (2017) 16:167 Page 3 of 9 Table 1 Clinical and biochemical characteristics of the study subjects including apoM Healthy controls HLP PNS + HLP PNS-HLP Subjects, n 73 37 62 33 Demographics Age, years 40 ± 14 42 ± 8 39 ± 13 39 ± 14 (male/female) 40/32 23/14 36/26 20/13 Body–mass index, kg/m2 21.4 ± 1.81 22.5 ± 2.40 22.3 ± 2.0 22.2 ± 2.0 Lipid profile: Triglycerides, mmol/L 0.86 ± 0.38 3.46 ± 1.90aa 2.54 ± 1.57aacc 1.86 ± 1.18aabb Total cholesterol, mmol/L 4.19 ± 0.56 5.52 ± 0.90aa 8.54 ± 2.60aacc 5.47 ± 2.62aabb HDL-C, mmol/L 1.59 ± 0.48a 1.12 ± 0.31aa 1.40 ± 0.25ac 1.35 ± 0.45aa LDL-C, mmol/L 2.58 ± 0.49 3.68 ± 0.82aa 6.67 ± 2.50aacc 3.73 ± 2.28aabb
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