Luo Frank J-G, Patel Kajal P, Marquez Ilian O, Plummer Natalie S, Hostetter Thomas H, Meyer Timothy W
Department of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA 94303, USA.
Am J Kidney Dis. 2009 Jun;53(6):1042-9. doi: 10.1053/j.ajkd.2009.01.265. Epub 2009 Apr 25.
Protein-bound solutes are poorly cleared by means of conventional hemodialysis because protein binding limits the "free" solute concentration driving diffusion. This study tested the modeled prediction that clearances of bound solutes could be increased by increasing the dialyzer mass transfer area coefficient (K(o)A) and dialysate flow (Q(d)) to greater than the levels used in conventional practice.
Pilot crossover trial.
SETTING & PARTICIPANTS: 6 stable long-term hemodialysis patients.
Study participants underwent an experimental dialysis treatment in which K(o)A and Q(d) were increased by using 2 dialyzers in series and supplying each dialyzer with a Q(d) of 800 mL/min by using 2 dialysis machines. Experimental clearances were compared with those during a conventional treatment with a single dialyzer and Q(d) of 800 mL/min supplied by 1 machine.
Measured clearances of uremic solutes.
Clearances were measured for urea nitrogen and the bound solutes p-cresol sulfate, indoxyl sulfate, kynurenic acid, and hippurate.
Clearances for the bound solutes during conventional treatment were lower than for urea nitrogen (clearance values: urea nitrogen, 255 +/- 16 mL/min; p-cresol sulfate, 23 +/- 4 mL/min; indoxyl sulfate, 30 +/- 7 mL/min; kynurenic acid, 43 +/- 4 mL/min; and hippurate, 115 +/- 11 mL/min). Experimental treatment increased clearances of all solutes (clearance values: urea nitrogen, 318 +/- 19 mL/min; p-cresol sulfate, 37 +/- 6 mL/min; indoxyl sulfate, 46 +/- 8 mL/min; kynurenic acid, 73 +/- 7 mL/min; and hippurate, 165 +/- 17 mL/min). The magnitude of the increases in clearance was greater for bound solutes than for urea nitrogen (increase in clearance: urea nitrogen, 25% +/- 6%; p-cresol sulfate, 66% +/- 19%; indoxyl sulfate, 57% +/- 27%; kynurenic acid, 69% +/- 5%; and hippurate, 44% +/- 15%).
A longer term study would be required to determine whether increased dialytic clearance of bound solutes leads to a decrease in plasma solute levels.
Dialytic clearance of protein-bound solutes can be increased by increasing K(o)A and Q(d) to greater than conventional levels.
由于蛋白质结合会限制驱动扩散的“游离”溶质浓度,因此传统血液透析对与蛋白质结合的溶质清除效果不佳。本研究对以下模型预测进行了测试:通过将透析器传质面积系数(KoA)和透析液流量(Qd)增加到高于传统做法所使用的水平,可以提高结合溶质的清除率。
初步交叉试验。
6名稳定的长期血液透析患者。
研究参与者接受了一项实验性透析治疗,通过串联使用2个透析器并使用2台透析机为每个透析器提供800 mL/min的Qd,从而增加KoA和Qd。将实验清除率与使用单个透析器且由1台机器提供800 mL/min的Qd进行传统治疗时的清除率进行比较。
测量尿毒症溶质的清除率。
测量尿素氮以及结合溶质对甲酚硫酸盐、硫酸吲哚酚、犬尿酸和马尿酸盐的清除率。
传统治疗期间结合溶质的清除率低于尿素氮(清除率值:尿素氮为255±16 mL/min;对甲酚硫酸盐为23±4 mL/min;硫酸吲哚酚为30±7 mL/min;犬尿酸为43±4 mL/min;马尿酸盐为115±11 mL/min)。实验性治疗提高了所有溶质的清除率(清除率值:尿素氮为318±19 mL/min;对甲酚硫酸盐为37±6 mL/min;硫酸吲哚酚为46±8 mL/min;犬尿酸为73±7 mL/min;马尿酸盐为165±17 mL/min)。结合溶质清除率的增加幅度大于尿素氮(清除率增加:尿素氮为25%±6%;对甲酚硫酸盐为66%±19%;硫酸吲哚酚为57%±27%;犬尿酸为69%±5%;马尿酸盐为44%±15%)。
需要进行更长期的研究以确定结合溶质透析清除率的增加是否会导致血浆溶质水平降低。
通过将KoA和Qd增加到高于传统水平,可以提高与蛋白质结合溶质的透析清除率。