Sakai Yoshitada
Dialysis Products Business Division, Toray Medical Co. Ltd, Urayasu, Chiba, Japan.
Contrib Nephrol. 2011;173:137-147. doi: 10.1159/000329052. Epub 2011 Aug 8.
Forty years have passed since the polymethylmethacrylate (PMMA) membrane was first developed. This article reviews its history and explains its longevity. The membrane was developed through application of a stereocomplex phenomenon that is observed upon mixture of isotactic and syndiotactic PMMA polymers. Filtryzer(TM) B1 and B2 were approved in Japan in 1977. B1 was the pioneer high-performance membrane model and B2 was a model that simulated a low-flux cellulosic membrane. The development of B1 led to the development of the dialysis machine with an ultrafiltration rate (UFR)-controlling function because the UFR of B1 was too high to control using transmembrane pressure control. B1 was used not only as a dialyzer but also as a hemodiafilter by combination with a UFR controller. Biocompatibility of the dialysis membrane, complement activation and/or transient leukopenia was studied with B2. Cooperative studies between Niigata University and Toray resulted in Gejyo's finding regarding the harmfulness of β(2)-microglobulin (BMG). Long-term follow-up of patients dialyzed using the BK membrane revealed that plasma BMG levels were significantly low and that the occurrence ratio of carpal tunnel syndrome was suppressed. These results were obtained by the adsorptive removal of BMG onto a PMMA membrane. Several papers have discussed new aspects in succession mainly based on clinical experiences that were not aimed at a development stage, i.e. they were kinds of serendipity. For the BK-F membrane with the largest pore size, this includes anemia and removal or modification of furancarboxylic acid, homocysteine, pentosidine and soluble CD40. For the BG membrane with a slightly anionic component, this includes pruritus and removal of free immunoglobulin light chains. Even patients' prognoses may be modified by the use of PMMA membrane. The mechanisms of these findings have been clarified bit by bit and the membrane will further open new frontiers in dialysis treatment.
聚甲基丙烯酸甲酯（PMMA）膜首次研发至今已有40年。本文回顾了其历史并解释了其经久不衰的原因。该膜是通过应用等规和间规PMMA聚合物混合时观察到的立体络合现象而开发的。Filtryzer(TM) B1和B2于1977年在日本获得批准。B1是开创性的高性能膜模型，B2是模拟低通量纤维素膜的模型。B1的开发促成了具有超滤率（UFR）控制功能的透析机的发展，因为B1的UFR过高，无法通过跨膜压力控制进行调节。B1不仅用作透析器，还通过与UFR控制器结合用作血液透析滤过器。用B2研究了透析膜的生物相容性、补体激活和/或短暂性白细胞减少。新潟大学和东丽公司的合作研究导致Gejyo发现了β2-微球蛋白（BMG）的危害。对使用BK膜进行透析的患者的长期随访表明，血浆BMG水平显著降低，腕管综合征的发生率也得到了抑制。这些结果是通过将BMG吸附到PMMA膜上获得的。几篇论文相继讨论了新的方面，主要基于并非处于开发阶段的临床经验，也就是说，它们有点像是意外发现。对于孔径最大的BK-F膜，这包括贫血以及糠羧酸、同型半胱氨酸、戊糖苷和可溶性CD40的去除或修饰。对于含有轻微阴离子成分的BG膜，这包括瘙痒和游离免疫球蛋白轻链的去除。甚至患者的预后也可能因使用PMMA膜而得到改善。这些发现的机制已逐渐得到阐明，该膜将在透析治疗中进一步开拓新的领域。
