Removal of uremic toxins by renal replacement therapies: a review of current progress and future perspectives

Accumulation of uremic toxins induces various uremia-related complications in patients with chronic kidney disease, particularly those undergoing dialysis treatment. Direct interactions of uremic toxins with organ tissues are thought to be a major pathophysiological mechanism for disease; for example, indoxyl sulfate reacts directly with macrophages and accelerates atherosclerosis. The removal of sufficient volume of uremic toxins will prevent uremia-related complications in dialysis patients. Hemodialysis with the use of a high-flux dialysis membrane, long or frequent treatment, and increased blood/dialysate flow has improved removal of water-soluble small molecular weight uremic toxins. Middle molecular weight molecules are removed more effectively with hemodialysis using a high-flux membrane, hemodiafiltration and hemofiltration, and a direct hemoperfusion method using β 2 -microglobulin adsorption column, which is useful in reducing serum β 2 -microglobulin levels as well as improving dialysis-related amyloidosis-induced clinical symptoms. With improvements in dialysis therapies, removal of low and middle molecular weight water-soluble molecules has improved; however, conventional dialysis treatment is limited in its ability to remove protein-bound uremic toxins (PBUTs). Recent findings suggest that adsorption treatments using oral charcoal adsorbent, mixed matrix membrane hollow fiber, and additive charcoal in the dialysate, in addition to conventional dialysis treatment, may effectively remove a substantial amount of PBUTs. Further improvement of renal replacement therapy, including dialysis and additional therapeutic strategies, is needed for better clearance of small and middle molecular weight molecules and PBUTs, which will lead to improved survival and quality of life for dialysis-dependent chronic kidney disease patients.