Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration
Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration
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DOI：
10.1093/ndt/gfp437
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发表时间：
2010-01-01
影响因子：
6.1
通讯作者：
Canaud, Bernard
中科院分区：
文献类型：
--
作者：
Krieter, Detlef H.;Hackl, Andrea;Canaud, Bernard
方法。两种类型的聚醚砜膜仅在白蛋白通透性不同（称为PU-和PU+）在8例维持透析患者中进行前瞻性交叉比较。个别患者的治疗设置相同：时间229 +/- 22分钟；血流量378 +/- 33 mL/min；透析液流速500 mL/min；血液滤过取代流率94 +/- 9ml /min。通过还原比（rr）、透析间隙和连续收集的透析液质量来测定蛋白质结合化合物对甲酰硫酸酯（pCS）和吲哚酚硫酸酯（IS）的去除。同时测定低分子量（LMW）蛋白β(2)-微球蛋白、胱抑素c、肌红蛋白（myo）、游离视黄醇结合蛋白（rbp）和白蛋白的消除。血浆蛋白结合毒素水平在所有治疗形式下均显著降低。然而，透析膜之间以及血液透析和血液滤过之间的降低是相似的。总pc的rr介于40.4 +/- 25.3和47.8 +/- 10.3%之间，总IS介于50.4 +/- 2.6和54.6 +/- 8.7%之间。透析液中游离蛋白结合毒素的消除与预处理前血浆浓度密切相关，总pc和总IS的浓度分别为r = 0.920 （P < 0.001）和r = 0.906 （P < 0.001）。与血液透析相比，血液滤过对所有LMW蛋白的去除要高得多。透析膜的差异仅在血液透析中表现为较大的LMW蛋白myo和rbp，而PU+的rbp比PU+高（myo为46 +/- 9比37 +/- 9%；rbp为18 +/- 5比15 +/- 5%；P < 0.05）。此外，不同膜和处理方式的白蛋白损失也不同，血液透析中PU-检测不到白蛋白损失，血液滤过中PU+检测到的白蛋白损失最高（1430 +/- 566 mg）。透析液中蛋白结合化合物的消除可以通过预处理血浆浓度水平来预测，并特别依赖于扩散。在线稀释后血液渗透缺乏增强的去除，强调对流对这些溶质的清除的次要意义。与LMW蛋白相比，所有的治疗形式都不能有效地消除高蛋白结合毒素pCS和IS。对于持续降低pCS和IS血浆水平，替代策略有望成为更有效的治疗形式。
Methods. Two types of polyethersulfone membranes only differing in albumin permeability (referred as PU- and PU+) were compared in eight patients on maintenance dialysis in a prospective cross-over manner. Treatment settings were identical for individual patients: time 229 +/- 22 min; blood flow rate 378 +/- 33 mL/min; dialysate flow rate 500 mL/min; substitution flow rate in haemodiafiltration 94 +/- 9 mL/min. Removal of the protein-bound compounds p-cresyl sulfate (pCS) and indoxyl sulfate (IS) was determined by reduction ratios (RRs), dialytic clearances and mass in continuously collected dialysate. In addition, the elimination of the low-molecular weight (LMW) proteins beta(2)-microglobulin, cystatin c, myoglobin (myo), free retinol-binding protein (rbp) and albumin was measured.Results. Plasma levels of the protein-bound toxins were significantly decreased by all treatment forms. However, the decreases were comparable between dialysis membranes and between haemodialysis and haemodiafiltration. The RRs of total pCS ranged between 40.4 +/- 25.3 and 47.8 +/- 10.3% and of total IS between 50.4 +/- 2.6 and 54.6 +/- 8.7%. Elimination of free protein-bound toxins as assessed by their mass in dialysate closely correlated positively with the pre-treatment plasma concentrations being r = 0.920 (P < 0.001) for total pCS and r = 0.906 (P < 0.001) for total IS, respectively. Compared to haemodialysis, much higher removal of all LMW proteins was found in haemodiafiltration. Dialysis membrane differences were only obvious in haemodialysis for the larger LMW proteins myo and rbp yielding significantly higher RRs for PU+ (myo 46 +/- 9 versus 37 +/- 9%; rbp 18 +/- 5 versus 15 +/- 5%; P < 0.05). Additionally, the albumin loss varied between membranes and treatment modes being undetectable with PU- in haemodialysis and highest with PU+ in haemodiafiltration (1430 +/- 566 mg).Conclusions. The elimination of protein-bound compounds into dialysate is predicted by the level of pre-treatment plasma concentrations and depends particularly on diffusion. Lacking enhanced removal in online post-dilution haemodiafiltration emphasizes the minor significance of convection for the clearance of these solutes. Compared to LMW proteins, the highly protein-bound toxins pCS and IS are less effectively eliminated with all treatment forms. For a sustained decrease of pCS and IS plasma levels, alternative strategies promise to be more efficient therapy forms.