Improved Dialysis Removal of Protein-Bound Uraemic Toxins with a Combined Displacement and Adsorption Technique
Improved Dialysis Removal of Protein-Bound Uraemic Toxins with a Combined Displacement and Adsorption Technique
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结合置换和吸附技术改进透析去除蛋白质结合的尿毒症毒素
DOI：
10.1159/000518065
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发表时间：
2021-08-16
影响因子：
3
通讯作者：
Ding, Feng
中科院分区：
文献类型：
--
作者：
Shi, Yuanyuan;Tian, Huajun;Ding, Feng
简介：由于蛋白结合尿毒症毒素 (PBUT) 血浆蛋白结合率高，因此游离（可透析）血浆浓度较低，因此传统透析技术很难去除它们。在这里，我们在体外和体内评估和比较了传统血液透析 (HD)、基于吸附的 HD、基于置换的 HD 及其 2 种组合的 PBUT 去除率。方法：首先在体外单通道 HD 模型中评估 PBUT 的去除，包括 3-羧基-4-甲基-5-丙基-2-呋喃-丙酸 (CMPF)、对甲酚硫酸盐 (PCS)、硫酸吲哚酚 (IS)、吲哚-3-乙酸 (3-IAA) 和马尿酸。吸附包括向透析液中添加 40 g/L 牛血清白蛋白 (Alb)，置换涉及在预透析器中注入脂肪酸 (FA) 混合物。然后，尿毒症大鼠接受常规 HD、基于 Alb 的 HD、基于脂肪乳输注的 HD 或其组合治疗，计算治疗 4 h 后溶质的减少率 (RR) 和总溶质去除量 (TSR)。结果：体外透析显示，与基线相比，FAs 输注预过滤器对 PCS、IS 和 3-IAA 的去除率分别提高了 3.23 倍、3.01 倍和 2.24 倍，并将 CMPF 的去除率从基线时不可检测到的提高到 14.33 ± 0.24%，透析效果明显优于 Alb 透析。体内透析显示，与对照组相比，在 HD 4 小时后，基于 ω-6 大豆油的脂肪乳给药导致 PCS、IS 和 3-IAA 的 RR 和 TSR 更高，并且与 Alb 透析相比，PCS 和 IS 相应的 TSR 值也显着增加。最后，在体外和体内结合使用它们时，始终观察到去除高度结合的溶质的最高透析效率。结论：基于置换和吸附的透析相结合的概念可能会在透析领域开辟新的途径和可能性，以进一步增强终末期肾病中 PBUT 的去除。
Introduction: Protein-bound uraemic toxins (PBUTs) are poorly removed by conventional dialytic techniques, given their high plasma protein binding, and thus low, free (dialysable) plasma concentration. Here, we evaluated and compared PBUTs removal among conventional haemodialysis (HD), adsorption-based HD, displacement-based HD, and their 2 combinations both in vitro and in vivo. Methods: The removal of PBUTs, including 3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresyl sulphate (PCS), indoxyl sulphate (IS), indole-3-acetic acid (3-IAA), and hippuric acid, was first evaluated in an in vitro single-pass HD model. Adsorption consisted of adding 40 g/L bovine serum albumin (Alb) to the dialysate and displacement involved infusing fatty acid (FA) mixtures predialyser. Then, uraemic rats were treated with either conventional HD, Alb-based HD, lipid emulsion infusion-based HD or their combination to calculate the reduction ratio (RR), and the total solute removal (TSR) of solutes after 4 h of therapy. Results: In vitro dialysis revealed that FAs infusion prefilter increased the removal of PCS, IS, and 3-IAA 3.23-fold, 3.01-fold, and 2.24-fold, respectively, compared with baseline and increased the fractional removal of CMPF from undetectable at baseline to 14.33 ± 0.24%, with a dialysis efficacy markedly superior to Alb dialysis. In vivo dialysis showed that ω-6 soybean oil-based lipid emulsion administration resulted in higher RRs and more TSRs for PCS, IS, and 3-IAA after 4-h HD than the control, and the corresponding TSR values for PCS and IS were also significantly increased compared to that of Alb dialysis. Finally, the highest dialysis efficacy for highly bound solute removal was always observed with their combination both in vitro and in vivo. Conclusions: The concept of combined displacement- and adsorption-based dialysis may open up new avenues and possibilities in the field of dialysis to further enhance PBUTs removal in end-stage renal disease.