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首页> 外文期刊>Scientific reports. >In silico comparison of protein-bound uremic toxin removal by hemodialysis, hemodiafiltration, membrane adsorption, and binding competition
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In silico comparison of protein-bound uremic toxin removal by hemodialysis, hemodiafiltration, membrane adsorption, and binding competition

机译：在计算机上比较通过血液透析，血液透析滤过，膜吸附和结合竞争去除结合蛋白的尿毒症毒素

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Protein-bound uremic toxins (PBUTs) are poorly removed during hemodialysis (HD) due to their low free (dialyzable) plasma concentration. We compared PBUT removal between HD, hemodiafiltration (HDF), membrane adsorption, and PBUT displacement in HD. The latter involves infusing a binding competitor pre-dialyzer, which competes with PBUTs for their albumin binding sites and increases their free fraction. We used a mathematical model of PBUT/displacer kinetics in dialysis comprising a three-compartment patient model, an arterial/venous tube segment model, and a dialyzer model. Compared to HD, improvements in removal of prototypical PBUTs indoxyl sulfate (initial concentration 100?μM, 7% free) and p-cresyl sulfate (150?μM, 5% free) were: 5.5% and 6.4%, respectively, for pre-dilution HDF with 20?L replacement fluid; 8.1% and 9.1% for post-dilution HDF 20?L; 15.6% and 18.3% for pre-dilution HDF 60?L; 19.4% and 22.2% for complete membrane adsorption; 35.0% and 41.9% for displacement with tryptophan (2000 mg in 500?mL saline); 26.7% and 32.4% for displacement with ibuprofen (800?mg in 200?mL saline). Prolonged (one-month) use of tryptophan reduces the IS and pCS time-averaged concentration by 28.1% and 29.9%, respectively, compared to conventional HD. We conclude that competitive binding can be a pragmatic approach for improving PBUT removal.
机译：蛋白结合的尿毒症毒素（PBUT）在血液透析（HD）期间由于其游离（可透析）血浆浓度低而很难去除。我们比较了HD，血液透析滤过（HDF），膜吸附和HD中PBUT置换之间的PBUT去除。后者涉及注入结合竞争对手的预透析器，该透析器与PBUT竞争其白蛋白结合位点并增加其游离分数。我们在透析中使用了PBUT /置换器动力学的数学模型，包括三房患者模型，动脉/静脉管段模型和透析器模型。与HD相比，原型PBUTs去除吲哚基硫酸盐（初始浓度100？μM，游离7％）和对甲苯基硫酸盐（150？μM，游离5％）的改进分别为：5.5％和6.4％。用20？L替代液稀释HDF;稀释后HDF 20？L的8.1％和9.1％;稀释前HDF 60？L的15.6％和18.3％; 19.4％和22.2％的膜完全吸附;色氨酸（2000 mg溶于500？mL盐水）的置换率为35.0％和41.9％;用布洛芬（800？mg在200？mL盐水中）置换的剂量分别为26.7％和32.4％。与常规HD相比，长时间（一个月）使用色氨酸可使IS和pCS时间平均浓度分别降低28.1％和29.9％。我们得出结论，竞争性结合可以是提高PBUT去除率的实用方法。

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