From uremic toxin retention to removal by convection: do we know enough?

The uremic syndrome is defined by a complex clinical picture, characterized by the dysfunction of most organs which are affected by the retention of multiple solutes. Recent research has helped to unravel the pathophysiology and to identify several as yet unknown responsible compounds. In this publication, we summarize which compounds play the most important pathophysiologic role, and which dialysis strategies can be considered to decrease their concentration and improve outcomes. The main pathophysiologic role is played by molecules which are so-called 'difficult to remove by dialysis'. Essentially observational studies have suggested that enhancement of removal of these molecules, by improving convection (hemodiafiltration), creates an improvement of survival. The knowledge of uremic toxicity is still far from complete however, and we need extra information about responsible compounds and mechanisms, eventually leading to a classification of the most important culprits, to allow the development of even more efficient or specific removal strategies.