Ćwiklińska Agnieska, Cackowska Monika, Wieczorek Ewa, Król Ewa, Kowalski Robert, Kuchta Agnieszka, Kortas-Stempak Barbara, Gliwińska Anna, Dąbkowski Kamil, Zielińska Justyna, Dębska-Ślizień Alicja, Jankowski Maciej
Department of Clinical Chemistry, Medical University of Gdańsk, Gdańsk, Poland,
Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdańsk, Gdańsk, Poland.
Kidney Blood Press Res. 2018;43(3):970-978. doi: 10.1159/000490686. Epub 2018 Jun 15.
BACKGROUND/AIMS: Hypertriglyceridaemia (HTG) and reduction and dysfunction of high density lipoprotein (HDL) are common lipid disturbances in chronic kidney disease (CKD). HTG in CKD is caused mainly by the decreased efficiency of lipoprotein lipase (LPL)-mediated very low density lipoprotein triglyceride (VLDL-TG) lipolysis. It has not been clarified whether HDL dysfunction in CKD contributes directly to HTG development; thus, the aim of this study was to assess the impact of CKD progression on the ability of HDL to enhance LPL-mediated VLDL-TG lipolysis efficiency.
VLDL was isolated from non-dialysis patients in CKD stages 3 and 4 and from non-CKD patients. The VLDL was incubated with LPL at the constant LPL:VLDL-TG ratio, in the absence or presence of HDL. After incubation, the VLDL was separated and the percentage (%) of hydrolyzed TG was calculated.
HDL presence increased the lipolysis efficiency of VLDL isolated from CKD and non-CKD patients, for the VLDL-TG> 50 mg/dl. Its effect was dependent on the VLDL-TG and HDL-cholesterol concentrations in the reaction mixtures: the higher the concentrations of VLDL-TG and HDL-cholesterol, the greater the effect. The positive impact of HDL on VLDL lipolysis was modified by CKD progression: the percentage of lipolyzed VLDL-TG in the presence of HDL decreased with a reduction in eGFR (r=0.43, p=0.009), and for patients with stage 4 CKD, no positive impact of HDL on lipolysis was observed. The percentage of lipolyzed TG correlated negatively with apoE and apoCs content in VLDL, and positively with HDL-apoCII, as well as with VLDL and HDL apoCII/ apoCIII ratios. The progression of CKD was associated with unfavourable changes in VLDL and HDL composition; apoE and apoCs levels increased in VLDL with a decrease in eGFR whereas the HDL-cholesterol level decreased.
The progression of CKD affects lipoprotein composition and properties, and modulates the positive impact of HDL on VLDL lipolysis efficiency. In CKD patients, HDL deficiency and dysfunction can directly affect hypertriglyceridaemia development.
背景/目的：高甘油三酯血症（HTG）以及高密度脂蛋白（HDL）水平降低和功能障碍是慢性肾脏病（CKD）常见的脂质紊乱情况。CKD中的HTG主要由脂蛋白脂肪酶（LPL）介导的极低密度脂蛋白甘油三酯（VLDL-TG）脂解效率降低所致。目前尚不清楚CKD中的HDL功能障碍是否直接导致HTG的发生；因此，本研究的目的是评估CKD进展对HDL增强LPL介导的VLDL-TG脂解效率能力的影响。
从CKD 3期和4期的非透析患者以及非CKD患者中分离VLDL。将VLDL在LPL与VLDL-TG比例恒定的情况下，于不存在或存在HDL的条件下与LPL一起孵育。孵育后，分离VLDL并计算水解甘油三酯的百分比（%）。
对于VLDL-TG>50mg/dl的情况，HDL的存在提高了从CKD和非CKD患者中分离出的VLDL的脂解效率。其作用取决于反应混合物中VLDL-TG和HDL胆固醇的浓度：VLDL-TG和HDL胆固醇的浓度越高，作用越大。HDL对VLDL脂解的积极影响因CKD进展而改变：在存在HDL的情况下，脂解的VLDL-TG百分比随着估算肾小球滤过率（eGFR）的降低而降低（r=0.43，p=0.009），并且对于4期CKD患者，未观察到HDL对脂解有积极影响。脂解甘油三酯的百分比与VLDL中的载脂蛋白E（apoE）和载脂蛋白C（apoCs）含量呈负相关，与HDL-载脂蛋白CII（HDL-apoCII）呈正相关，也与VLDL和HDL的apoCII/apoCIII比值呈正相关。CKD的进展与VLDL和HDL组成的不利变化相关；随着eGFR降低，VLDL中的apoE和apoCs水平升高，而HDL胆固醇水平降低。
CKD的进展会影响脂蛋白的组成和性质，并调节HDL对VLDL脂解效率的积极影响。在CKD患者中，HDL缺乏和功能障碍可直接影响高甘油三酯血症的发生。
