Eloot Sunny, Schneditz Daniel, Cornelis Tom, Van Biesen Wim, Glorieux Griet, Dhondt Annemie, Kooman Jeroen, Vanholder Raymond
Nephrology Section, Department of Internal Medicine, Ghent University Hospital, Gent, Belgium.
Institute of Physiology, Medical University of Graz, Graz, Austria.
PLoS One. 2016 Jan 22;11(1):e0147159. doi: 10.1371/journal.pone.0147159. eCollection 2016.
We studied various hemodialysis strategies for the removal of protein-bound solutes, which are associated with cardiovascular damage.
This study included 10 patients on standard (3 x 4 h/week) high-flux hemodialysis. Blood was collected at the dialyzer inlet and outlet at several time points during a midweek session. Total and free concentration of several protein-bound solutes was determined as well as urea concentration. Per solute, a two-compartment kinetic model was fitted to the measured concentrations, estimating plasmatic volume (V1), total distribution volume (V tot) and intercompartment clearance (K21). This calibrated model was then used to calculate which hemodialysis strategy offers optimal removal. Our own in vivo data, with the strategy variables entered into the mathematical simulations, was then validated against independent data from two other clinical studies.
Dialyzer clearance K, V1 and V tot correlated inversely with percentage of protein binding. All Ks were different from each other. Of all protein-bound solutes, K21 was 2.7-5.3 times lower than that of urea. Longer and/or more frequent dialysis that processed the same amount of blood per week as standard 3 x 4 h dialysis at 300 mL/min blood flow showed no difference in removal of strongly bound solutes. However, longer and/or more frequent dialysis strategies that processed more blood per week than standard dialysis were markedly more adequate. These conclusions were successfully validated.
When blood and dialysate flow per unit of time and type of hemodialyzer are kept the same, increasing the amount of processed blood per week by increasing frequency and/or duration of the sessions distinctly increases removal.
我们研究了多种用于清除与心血管损伤相关的蛋白结合溶质的血液透析策略。
本研究纳入了10例接受标准(每周3次,每次4小时)高通量血液透析的患者。在周中透析 session 的几个时间点,于透析器入口和出口采集血液。测定了几种蛋白结合溶质的总浓度和游离浓度以及尿素浓度。对于每种溶质,将二室动力学模型拟合到测量浓度,估算血浆容积(V1)、总分布容积(V tot)和室间清除率(K21)。然后使用这个校准模型来计算哪种血液透析策略能实现最佳清除效果。接着,我们将输入了策略变量的自身体内数据与另外两项临床研究的独立数据进行了验证。
透析器清除率K、V1和V tot与蛋白结合百分比呈负相关。所有的K值彼此不同。在所有蛋白结合溶质中,K21比尿素的K21低2.7至5.3倍。每周处理相同血量(与标准的每周3次、每次4小时、血流速度300 mL/min的透析相同)的更长时间和/或更频繁的透析,在清除强结合溶质方面没有差异。然而,每周处理血量比标准透析更多的更长时间和/或更频繁的透析策略明显更充分。这些结论得到了成功验证。
当单位时间内的血液和透析液流量以及血液透析器类型保持相同时,通过增加透析频率和/或时长来增加每周处理的血量,可显著提高清除效果。