Dominik Adrian, Stange Jan, Pfensig Claudia, Borufka Luise, Weiss-Reining Helga, Eggert Martin
Center for Extracorporeal Organ Support, Department of Internal Medicine, University of Rostock, Rostock, Germany.
Ther Apher Dial. 2014 Aug;18(4):347-52. doi: 10.1111/1744-9987.12146. Epub 2013 Nov 12.
The removal of small water soluble toxins and albumin-bound toxins in acute liver failure patients (ALF) or acute-on-chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e.g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut-offs should be considered in extracorporeal liver support devices based on albumin dialysis in order to address these problems, as the introduction of super-large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment albumin dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin-bound toxins were removed more efficiently using novel large (Emic2) to super-large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL-6 and tumor necrosis factor-α was drastically improved using super-large pore membranes. The Emic2 membrane predominantly removed IL-6. In vitro data suggest that the usage of larger pore sized membranes in albumin dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super-large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified.
使用体外肝脏支持设备(如分子吸附循环系统;MARS)已证实可清除急性肝衰竭(ALF)患者或慢加急性肝衰竭(AocLF)患者体内的小水溶性毒素和与白蛋白结合的毒素。然而,使用MARS降低ALF/AocLF患者体内升高的细胞因子水平的效果仍不够显著,无法有效降低患者血清细胞因子水平。基于白蛋白透析的体外肝脏支持设备应考虑采用孔径更大或截留值更高的新型膜,以解决这些问题,因为引入超大孔膜可抵消细胞因子的高产生率,并进一步改善体内解毒效果。利用已建立的体外双室白蛋白透析模型,将三种不同孔径的新型膜与MARS Flux膜在体外进行细胞因子清除和解毒质量的比较。比较这些膜后发现,水溶性毒素的清除没有改善。使用新型大孔径(Emic2)至超大孔径膜(S20;甘布罗碳酸氢盐膜)能更有效地清除与白蛋白结合的毒素。使用超大孔膜可显著提高细胞因子IL-6和肿瘤坏死因子-α的清除率。Emic2膜主要清除IL-6。体外数据表明,在白蛋白透析中使用更大孔径的膜可有效降低升高的细胞因子水平和肝衰竭毒素。使用大孔径至超大孔径膜可能会对患者血清细胞因子水平产生影响。结合增强的解毒作用,这可能会提高ALF/AocLF患者的生存率。已确定了有前景的用于临床评估的膜。