Baxter International, Research and Development, Hechingen, Germany.
Nelson, New Zealand.
Nephrol Dial Transplant. 2018 Oct 1;33(suppl_3):iii22-iii27. doi: 10.1093/ndt/gfy228.
Modern methods in analytical biochemistry have established that uraemia is associated with the retention of proteins, both in their native state and post-translationally modified, over a wide range of molecular weights up to 60 kDa. Evidence is accumulating that these higher molecular weight retention solutes are important uraemic toxins, and therapies such as online haemodiafiltration (HDF), which enhance their removal, are associated with improved outcomes. However, HDF has limitations regarding cost, clinical implementation and the need for an external source of sterile substitution solution to maintain fluid balance. New membranes that have a solute removal profile more closely approaching that of the glomerular filtration barrier when used for conventional haemodialysis, while at the same time not allowing the passage of clinically significant amounts of beneficial proteins, are needed to address these limitations. Tighter control of the molecular characteristics of the polymers used for membrane fabrication, along with the introduction of additives and improvements in the manufacturing process, has led to membranes with a tighter pore size distribution that allows the use of an increased absolute pore size without leaking substantial amounts of albumin. At the same time, the wall thickness and internal diameter of membrane fibres have been decreased, enhancing convective transport within the dialyser without the need for an external source of substitution solution. These new expanded range membranes provide a solute removal profile more like that of the native kidney than currently available membranes when used in conventional haemodialysis.
现代分析生物化学方法已经证实,尿毒症与蛋白质的保留有关,无论是在天然状态还是翻译后修饰状态,分子量范围很广,高达 60 kDa。有证据表明,这些高分子量保留溶质是重要的尿毒症毒素,而在线血液透析滤过(HDF)等增强其清除的治疗方法与改善结果相关。然而,HDF 在成本、临床实施以及维持液体平衡所需的无菌替代溶液外部来源方面存在局限性。需要新的膜,当用于常规血液透析时,其溶质清除特性更接近肾小球滤过屏障,同时不允许有临床意义量的有益蛋白质通过,以解决这些局限性。通过更严格地控制用于膜制造的聚合物的分子特性,以及添加添加剂和改进制造工艺,已经生产出具有更紧密的孔径分布的膜,允许使用更大的绝对孔径而不会泄漏大量白蛋白。同时,膜纤维的壁厚和内径减小了,在不需要外部替代溶液源的情况下增强了透析器内的对流传输。与目前可用的膜相比,当这些新型扩展范围的膜用于常规血液透析时,提供的溶质清除特性更接近天然肾脏。