Kobayashi Shuzo
Department of Nephrology, and Kidney & Dialysis Center, Shonan Kamakura General Hospital, 1202-1 Yamazaki, Kamakura 247-8533, Japan.
Clin Exp Nephrol. 2008 Feb;12(1):9-15. doi: 10.1007/s10157-007-0003-8. Epub 2008 Jan 5.
LDL-apheresis (LA) was originally used for familial hyperlipidemia, and then in Japan extended to use for the treatment of patients with peripheral arterial disease (PAD) and nephrotic syndrome due to steroid-resistant focal glomerular sclerosis (FGS). The reason why this treatment is applicable for these disorders is due to the fact that LA exerts its favorable effects beyond the lipid-lowering effect. The main underlying mechanisms, for example, in the case of LA application in patients with PAD are: (1) improvement of hemorheology, (2) improvement of endothelial dysfunction, (3) elevations of serum levels of NO and bradykinin, (4) increase in serum levels of vascular endothelial growth factor, and (5) reduction of adhesion molecules on monocytes. Furthermore, we have reported that LA could have anti-inflammatory effects because LA reduces serum levels of P-selectin, which is known to play an important role in the development of atherosclerosis as well as a reduction of serum C-reactive protein levels as standard biomarker of atherosclerosis. Massive proteinuria is also an important challenge in nephrology. The possible mechanisms besides removal of toxic lipids are the reduction of the vasoconstrictive prostanoid and thromboxane A2 (TXA2) and an improvement in macrophage function evidenced by a significant amelioration of interleukin-8 production by lipopolysaccharide-stimulated peripheral blood mononuclear cells. It is intriguing to note that in terms of pharmacodynamics, LA improves steroid and cyclosporine uptake into lymphocytes. Although there are no randomized controlled trials, it is clear that LA has various effects beyond lowering lipids. Making the device more concise and changing it into a whole blood adsorption type, we need to collect more clinical cases and to study the underlying mechanisms further.
低密度脂蛋白清除术（LA）最初用于家族性高脂血症，随后在日本扩展至用于治疗外周动脉疾病（PAD）患者以及因类固醇抵抗性局灶节段性肾小球硬化（FGS）所致的肾病综合征。这种治疗适用于这些疾病的原因在于LA除了具有降脂作用外还能发挥有益效应。例如，在PAD患者中应用LA的主要潜在机制有：（1）改善血液流变学；（2）改善内皮功能障碍；（3）提高血清一氧化氮（NO）和缓激肽水平；（4）增加血清血管内皮生长因子水平；（5）降低单核细胞上的黏附分子。此外，我们报道过LA可能具有抗炎作用，因为LA可降低血清P选择素水平，已知P选择素在动脉粥样硬化发展中起重要作用，同时还能降低作为动脉粥样硬化标准生物标志物的血清C反应蛋白水平。大量蛋白尿也是肾脏病学中的一个重要挑战。除了清除毒性脂质外，可能的机制还包括降低血管收缩性前列腺素和血栓素A2（TXA2）以及改善巨噬细胞功能，脂多糖刺激的外周血单个核细胞产生白细胞介素-8显著改善可证明这一点。值得注意的是，在药效学方面，LA可改善类固醇和环孢素进入淋巴细胞的摄取。尽管尚无随机对照试验，但很明显LA除了降低血脂外还有多种作用。为使设备更简洁并将其转变为全血吸附型，我们需要收集更多临床病例并进一步研究潜在机制。
