Enhancing dialyser clearance—from target to development

Abstract

Products of metabolism accumulate in kidney failure and potentially have toxic effects. Traditionally these uraemic toxins are classified as small, middle-sized and protein-bound toxins, and clearance during dialysis is affected by diffusion, convection and adsorption. As current dialysis practice effectively clears small solutes, increasing evidence supports a toxic effect for middle-sized and protein-bound toxins. Therefore, newer approaches to standard dialysis practice are required to look beyond urea clearance. Current dialysers have been developed to effectively clear small solutes and secondly to increase middle-sized toxin clearances. However, there is no ideal dialyser which can effectively clear all uraemic toxins. Advances in nanotechnology have led to improvements in manufacturing, with the production of smoother membrane surfaces and uniformity of pore size. The introduction of haemodiafiltration has led to changes in dialyser design to improve convective clearances. Both diffusional and convectional clearances can be increased by changing dialyser designs to alter blood and dialysate flows, and novel dialyser designs using microfluidics offer more efficient solute clearances. Adjusting surface hydrophilicity and charge alter adsorptive properties, and greater clearance of protein-bound toxins can be achieved by adding carbon or other absorptive monoliths into the circuit or by developing composite dialyser membranes. Other strategies to increase protein-bound toxins clearances have centred on disrupting binding and so displacing toxins from proteins. Just as the hollow fibre design replaced the flat plate dialyser, we are now entering a new era of dialyser designs aimed to increase the spectrum of uraemic toxins which can be cleared by dialysis.