Moving beyond small solute clearance: What evidence is there for more permeable dialyzers and haemodiafiltration?

Dialyzers were initially developed for diffusive clearance of uraemic toxins. Diffusion most effectively clears small uncharged solutes from plasma water, such as urea. Sessional urea clearance targets have been shown to be important for short-term patient survival, but over the longer term, although low-flux dialysis can prolong patient survival, accumulation of middle-sized uraemic toxins, such as β2 microglobulin can lead to disabling arthropathy. Although the introduction of high-flux dialyzers, designed to increase β2 microglobulin clearance, has reduced the prevalence of arthropathy; this has not been translated into a demonstrable significant improvement in patient survival. However, analysis of individual patients recruited into trials of haemo-diafiltration reported that greater convective clearance was associated with better survival, although the individual trials reported mixed outcomes. Most haemodiafiltration trials were not designed to study the effect of convective dose, so although reported patient survival was greater for those receiving greater convective volume exchange, these results could potentially be confounded by patient or center effects. An alternative approach to increasing middle-sized solute clearances would be to use more permeable dialyzers, but as yet there are no trials reporting survival with larger cutoff dialyzers. As such, although there is increasing evidence that increasing middle-sized molecular uraemic solute clearance is associated with improved patient survival, further prospective trials are required to determine whether as with Kt/Vurea there is a threshold effect of how much convective or middle-sized solute clearance is required to improve patient survival.