联合置换与吸附技术提高蛋白结合型尿毒症毒素的透析清除率。
Improved Dialysis Removal of Protein-Bound Uraemic Toxins with a Combined Displacement and Adsorption Technique.
机构信息
Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China,
Department of Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China,
出版信息
Blood Purif. 2022;51(6):548-558. doi: 10.1159/000518065. Epub 2021 Aug 16.
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.
简介
由于蛋白结合型尿毒症毒素（PBUTs）与血浆蛋白高度结合，导致其游离（可透析）血浆浓度较低，因此，常规透析技术对其的清除效果较差。本研究旨在评估和比较常规血液透析（HD）、基于吸附的 HD、基于置换的 HD 及其 2 种组合在体外和体内对 PBUTs 的清除效果。
方法
首先，我们在体外单次通过 HD 模型中评估了 PBUTs（包括 3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF）、对甲酚硫酸盐（PCS）、吲哚硫酸（IS）、吲哚-3-乙酸（3-IAA）和马尿酸）的清除效果。吸附作用是在透析液中添加 40 g/L 牛血清白蛋白（Alb），置换作用是在预滤器前输注脂肪酸（FA）混合物。然后，用常规 HD、Alb 基 HD、脂质乳剂输注基 HD 或其组合治疗尿毒症大鼠，计算治疗 4 小时后溶质的减少率（RR）和总溶质清除率（TSR）。
结果
体外透析显示，与基线相比，FA 预过滤输注使 PCS、IS 和 3-IAA 的清除率分别增加了 3.23 倍、3.01 倍和 2.24 倍，使 CMPF 的分数清除率从基线时的无法检测增加到 14.33±0.24%，透析效果明显优于 Alb 透析。体内透析显示，ω-6 大豆油基脂质乳剂给药后，与对照组相比，4 小时 HD 后 PCS、IS 和 3-IAA 的 RR 和 TSR 更高，且与 Alb 透析相比，PCS 和 IS 的 TSR 值也显著增加。最后，在体外和体内，高结合溶质清除的最高透析效果总是与它们的组合同时观察到。
结论
基于置换和吸附的透析联合概念可能为透析领域开辟新的途径和可能性，以进一步提高终末期肾病患者的 PBUTs 清除率。
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