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肝素会在血脂正常的终末期肾病患者血液透析期间诱发致动脉粥样硬化脂蛋白的蓄积。

Heparin induces an accumulation of atherogenic lipoproteins during hemodialysis in normolipidemic end-stage renal disease patients.

作者信息

Barbagallo Carlo M, Noto Davide, Cefalù Angelo B, Ganci Antonia, Giammarresi Carlo, Panno Donata, Cusumano Gaspare, Greco Massimiliano, Di Gaudio Francesca, Averna Maurizio R

机构信息

Biomedical Department of Internal Medicine and Specialistics (DIBIMIS), University of Palermo, Palermo, Italy.

Division of Nephrology, Civic Hospital, Palermo, Italy.

出版信息

Hemodial Int. 2015 Jul;19(3):360-7. doi: 10.1111/hdi.12250. Epub 2014 Dec 12.

DOI:10.1111/hdi.12250
PMID:25495659
Abstract

Dyslipidemias may account for the excess of cardiovascular mortality in end-stage renal disease (ESRD). Lipoprotein studies in ESRD patients are usually relative to prehemodialysis samples even if significative changes may occur after dialysis. In this study, we aimed to investigate the effects of ESRD on triglyceride-rich lipoproteins (TRL) subpopulations distribution and acute change following hemodialytic procedures, including the relative contribution of heparin administration. We selected a group of normolipidemic male middle-aged ESRD patients free of any concomitant disease affecting lipoprotein remnant metabolism compared with controls. We separated TRL subfractions according to density and apoE content and evaluated the changes of these particles after hemodialytic procedures with or without heparin. ESRD subjects had higher TRL subfractions, with the exception of apoE-rich particles, lower high-density lipoprotein (HDL) largest subclasses, and a smaller low-density lipoprotein peak particle size than controls. After a hemodialytic standard procedure with heparin, we demonstrated a significant reduction of triglyceride, an increase of HDL-cholesterol levels, and a raise of small very-low-density lipoprotein, intermediate-density lipoproteins (IDL), apoE-rich particles, and non-HDL-cholesterol levels. When hemodialysis was performed without heparin, no significant changes were observed. In the absence of concomitant hyperlipidemic triggers, ESRD patients show significant lipoprotein abnormalities before dialysis, but without any increased remnant particles concentrations. We speculate that hemodialysis, in particular heparin administration during this procedure, leads to a massive atherogenic TRLs production because of the acute stimulation of the dysfunctional lipolytic system not followed by an efficient removal, determining a recurrent lipoprotein remnant accumulation.

摘要

血脂异常可能是终末期肾病(ESRD)中心血管死亡率过高的原因。ESRD患者的脂蛋白研究通常相对于血液透析前的样本,即使透析后可能会发生显著变化。在本研究中,我们旨在调查ESRD对富含甘油三酯的脂蛋白(TRL)亚群分布的影响以及血液透析程序后的急性变化,包括肝素给药的相对作用。我们选择了一组血脂正常的男性中年ESRD患者,与对照组相比,他们没有任何影响脂蛋白残粒代谢的伴随疾病。我们根据密度和载脂蛋白E含量分离TRL亚组分,并评估在有或没有肝素的血液透析程序后这些颗粒的变化。ESRD患者的TRL亚组分较高,但富含载脂蛋白E的颗粒除外,高密度脂蛋白(HDL)最大亚类较低,低密度脂蛋白峰值颗粒大小比对照组小。在使用肝素进行血液透析标准程序后,我们证明甘油三酯显著降低,HDL胆固醇水平升高,小极低密度脂蛋白、中间密度脂蛋白(IDL)、富含载脂蛋白E的颗粒和非HDL胆固醇水平升高。在不使用肝素进行血液透析时,未观察到显著变化。在没有伴随的高脂血症触发因素的情况下,ESRD患者在透析前表现出显著的脂蛋白异常,但没有任何残余颗粒浓度增加。我们推测,血液透析,特别是在此过程中给予肝素,由于功能失调的脂解系统受到急性刺激但没有有效清除,导致大量致动脉粥样硬化的TRL产生,从而导致脂蛋白残粒反复积累。

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