Tao Xia, Thijssen Stephan, Levin Nathan, Kotanko Peter, Handelman Garry
The Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts Lowell, Lowell, Mass., USA.
Blood Purif. 2015;39(4):323-30. doi: 10.1159/000381008. Epub 2015 May 14.
Indoxyl sulfate is a protein-bound uremic toxin and its dialytic clearance is comparatively low. We propose a method to increase indoxyl sulfate dialytic clearance.
Human serum albumin, preloaded with indoxyl sulfate, was circulated on the blood side of an F40S dialyzer with single-pass counter-current dialysate flow. Tryptophan or docosahexaenoic acid (DHA), which are binding competitors to indoxyl sulfate, were infused into the blood-side circuit upstream of the dialyzer, and their abilities to increase the removal of indoxyl sulfate determined.
Baseline indoxyl sulfate removal was 10.2 ± 0.3%, which increased to 18.5 ± 0.4% with infusion of tryptophan (p < 0.001) and 27.7 ± 1.0% with infusion of DHA (p < 0.001).
This study shows that tryptophan and DHA effectively increase indoxyl sulfate removal in an in vitro dialysis model. The concept of using binding competitors to enhance the clearance of protein-bound uremic toxins could be applied to current hemodialysis technology.
硫酸吲哚酚是一种与蛋白质结合的尿毒症毒素,其透析清除率相对较低。我们提出了一种提高硫酸吲哚酚透析清除率的方法。
预先加载硫酸吲哚酚的人血清白蛋白在具有单通道逆流透析液流的F40S透析器的血液侧循环。将作为硫酸吲哚酚结合竞争剂的色氨酸或二十二碳六烯酸(DHA)注入透析器上游的血液侧回路中,并测定它们提高硫酸吲哚酚清除率的能力。
硫酸吲哚酚的基线清除率为10.2±0.3%,注入色氨酸后增加至18.5±0.4%(p<0.001),注入DHA后增加至27.7±1.0%(p<0.001)。
本研究表明,在体外透析模型中,色氨酸和DHA能有效提高硫酸吲哚酚的清除率。使用结合竞争剂提高与蛋白质结合的尿毒症毒素清除率的概念可应用于当前的血液透析技术。