Increasing the Clearance of Protein-Bound Solutes by Recirculating Dialysate through Activated Carbon

Abstract

BackgroundConventional hemodialysis provides limited clearance of uremic solutes that bind to plasma proteins. However, no studies have tested whether increasing the clearance of bound solutes provides clinical benefit. Practical means to increase the dialytic clearance of bound solutes are required to perform such studies.MethodsArtificial plasma was dialyzed using two dialysis systems in series. In the first recirculating system, a fixed small volume of dialysate flowed rapidly through an activated carbon block before passing through two large dialyzers. In a second conventional system, a lower flow of fresh dialysate was passed through a single dialyzer. Chemical measurements tested the ability of the recirculating system to increase the clearance of selected solutes. Mathematical modeling predicted the dependence of solute clearances on the extent to which solutes were taken up by the carbon block and were bound to plasma proteins.ResultsBy itself, the conventional system provided clearances of the tightly bound solutes p-cresol sulfate and indoxyl sulfate of only 18±10 and 19±11 ml/min, respectively (mean±SD). Because these solutes were effectively adsorbed by the carbon block, the recirculating system by itself provided p-cresol sulfate and indoxyl sulfate clearances of 45±11 and 53±16 ml/min. It further raised their clearances to 54±12 and 61±17 ml/min when operating in series with the conventional system (P < 0.002 versus conventional clearance both solutes). Modeling predicted that the recirculating system would increase the clearances of bound solute even if their uptake by the carbon block was incomplete.ConclusionsWhen added to a conventional dialysis system, a recirculating system using a carbon block sorbent, a single pump, and standard dialyzers can greatly increase the clearance of protein-bound uremic solutes.