Enhanced Indoxyl Sulfate Dialyzer Clearance with the Use of Binding Competitors

Background: 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. Methods: 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. Results: 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). Conclusions: 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.