Division of Genetic Epidemiology, Department of Medical Genetics and Molecular Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
Clin J Am Soc Nephrol. 2013 Aug;8(8):1319-26. doi: 10.2215/CJN.10881012. Epub 2013 Apr 18.
In vivo metabolism of atherogenic apolipoprotein B (apoB)-containing lipoproteins is severely impaired in patients undergoing hemodialysis (HD), resulting in markedly prolonged residence times of these particles. It is unclear whether treatment with statins improves LDL kinetics in HD patients as is known for the general population. Therefore, this kinetic study assessed apoB-containing lipoproteins in these patients.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Kinetic measures were analyzed with stable-isotope technology in six men undergoing HD before and after 3 months of daily administration of 10 mg of atorvastatin. Patients were 18-65 years of age, had LDL cholesterol levels between 90 and 200 mg/dl, and had been treated with HD for >6 months. They consumed a standardized isocaloric diet for 3 days before analysis. Fractional catabolic rates (FCRs) and production rates of very-low-density lipoprotein (VLDL)-apoB, intermediate-density lipoprotein-apoB, and LDL-apoB were determined using multicompartment modeling after plasma lipoprotein separation, precipitation of apoB, and determination of tracer-to-tracee ratios using mass spectrometry.
Plasma concentrations of VLDL- and LDL-apoB were significantly lower (mean ± SD, 7.77±2.62 versus 11.27±6.15 mg/dl, P<0.05; 56.9±23.9 versus 84.0±21.1 mg/dl, P=0.03) and their FCRs were significantly higher (7.20±3.08 versus 5.20±2.98 days(-1), P<0.05; 0.851±0.772 versus 0.446±0.232 days(-1), P<0.05) after 3 months of atorvastatin treatment. Accordingly, the residence times in plasma of VLDL- and LDL-apoB were significantly lower after treatment (0.14 versus 0.19 day and 1.2 versus 2.2 days, respectively).
Lower plasma concentrations and improved kinetics of atherogenic lipoproteins were observed in HD patients after administration of low-dose atorvastatin.
进行血液透析（HD）的患者体内载脂蛋白 B（apoB）含脂蛋白的体内代谢严重受损，导致这些颗粒的停留时间明显延长。目前尚不清楚他汀类药物治疗是否像普通人群一样改善 HD 患者的 LDL 动力学。因此，这项动力学研究评估了这些患者的载脂蛋白 B 含脂蛋白。
设计、设置、参与者和测量：使用稳定同位素技术，在 6 名接受 HD 治疗的男性患者中进行了动力学测量，这些患者在接受每日 10mg 阿托伐他汀治疗 3 个月前后接受了评估。患者年龄在 18-65 岁之间，LDL 胆固醇水平在 90-200mg/dl 之间，且接受 HD 治疗超过 6 个月。在分析前，他们连续 3 天摄入标准化等热量饮食。使用多室模型在分离血浆脂蛋白、沉淀 apoB 以及使用质谱法测定示踪剂-示踪物比后，确定了极低密度脂蛋白（VLDL）-apoB、中间密度脂蛋白-apoB 和 LDL-apoB 的分数分解率（FCR）和生成率。
血浆 VLDL-和 LDL-apoB 浓度显著降低（平均值±SD，7.77±2.62 与 11.27±6.15mg/dl，P<0.05；56.9±23.9 与 84.0±21.1mg/dl，P=0.03），FCR 显著升高（7.20±3.08 与 5.20±2.98 天（-1），P<0.05；0.851±0.772 与 0.446±0.232 天（-1），P<0.05），阿托伐他汀治疗 3 个月后。因此，治疗后 VLDL-和 LDL-apoB 在血浆中的停留时间明显缩短（分别为 0.14 天与 0.19 天和 1.2 天与 2.2 天）。
HD 患者在接受低剂量阿托伐他汀治疗后，载脂蛋白 B 含脂蛋白的血浆浓度降低，动力学改善。
