Eloot Sunny, Ledebo Ingrid, Ward Richard A
Nephrology Section, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.
Scientific Affairs, Gambro R&D, Lund, Sweden.
Semin Nephrol. 2014 Mar;34(2):209-27. doi: 10.1016/j.semnephrol.2014.02.011. Epub 2014 Feb 18.
Improving outcomes by manipulating the prescription of renal replacement therapy to increase the removal of uremic toxins has had limited success. Failure to achieve better outcomes can be attributed to the heterogenic nature of uremic toxins, the complex distribution of some toxins in the body, and the predominant regimen of thee times weekly, in-center hemodialysis. This review summarizes the various mechanisms and kinetics of removal for the three major classes of uremic toxin-small water-soluble solutes, middle molecules, and protein-bound solutes-from both a theoretical and an experimental perspective. Taken together, the available data suggest that contemporary dialyzers are not a significant impediment to the removal of water-soluble uremic toxins, particularly when combined with commonly used blood and dialysis fluid flow rates and in online convective therapies. Enhancing the removal of those solutes will require a change in paradigm to longer and more frequent treatment sessions. Whether or not such a strategy also would improve the removal of protein-bound uremic toxins is less clear; that goal might require the development of different, more complex devices than those currently used for renal replacement therapy.
通过调整肾脏替代疗法的处方以增加尿毒症毒素清除来改善治疗效果的成效有限。未能取得更好的治疗效果可归因于尿毒症毒素的异质性、某些毒素在体内的复杂分布以及每周三次的中心血液透析的主要治疗方案。本综述从理论和实验角度总结了三类主要尿毒症毒素——小水溶性溶质、中分子和蛋白结合溶质——的各种清除机制和动力学。综合来看，现有数据表明，当代透析器并非水溶性尿毒症毒素清除的重大障碍，特别是与常用的血液和透析液流速相结合以及在在线对流治疗中。要增强这些溶质的清除，需要转变模式，采用更长且更频繁的治疗疗程。这种策略是否也能改善蛋白结合尿毒症毒素的清除尚不清楚；实现这一目标可能需要开发比目前用于肾脏替代治疗的设备更不同、更复杂的设备。
