Extracorporeal removal of uremic toxins: can we still do better?

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.