An adsorbent device to promote toxin removal during haemodialysis

When the kidneys fail they are no longer able to clear waste products which are normally cleared in urine. These molecules build up in the bloodstream and cause damage to other parts of the body.

In addition, kidney failure is associated with a sustained inflammatory state where substances which may cause cardiovascular disease and wasting are present in high quantities. Dialysis is a well-established treatment for patients with kidney failure.

However dialysis can only effectively remove small, water soluble waste products. Larger inflammatory molecules and those which are not water soluble and are bound to proteins accumulate over time and result in reduced life expectancy and quality of life. Although kidney dialysis treatments have been available for many years, Five year patient survival remains less than that for many common cancers, such as colon cancer. Thus new developments are required to improve patient outcome.

Many of the larger molecules which accumulate in patients with kidney failure can be removed by sticking them to a porous surface (termed adsorption). No cost effective and efficient adsorption devices are currently available. However, a range of advanced adsorbent materials have been recently developed which are able to remove these larger and protein bound compounds, and these can be produced relatively cheaply for use alongside haemodialysis without producing any harmful side effects. When fully tested these could enhance dialysis technology and offer a more effective therapy for patients with kidney failure.

Within the proof of concept DART project it was shown that nanoporous monoliths and beads could be used to a remove uraemic toxins not removed by HD alone. However, the synthesis route for the monolith prototypes was not appropriate for scale up of the device to a clinically relevant size.

Thus, the aim of the ADEPT project was:

> to optimise an adsorbent synthesis route allowing structural integrity on scale up of the nanoporous adsorbent material to a clinically useful size
> to assess the blood compatibility of the monolith adsorbents
> to assess the ability of the scaled up monolith adsorbent to adsorb uraemic toxins from healthy donor blood in a haemoperfusion circuit at haemodialysis flow rate.

A new synthesis route was developed to allow adsorbent monolith scale up whilst maintaining structural and adsorbent integrity. The monoliths were haemocompatible and maintained ability to adsorb key representative uraemic toxins which currently remain following haemodialysis.

The ADEPT device offers a cost effective product which once fully optimised could be used in line with current dialysis technology, potentially impacting the unacceptably high morbidity and mortality rates currently observed for haemodialysis patients.

SR Sandeman, CA Howell, GJ Phillips, Y Zheng, G Standen, R Pletzenauer, A Davenport, K Basnayake, O Boyd, S Holt, SV Mikhalovsky. (2014) An adsorbent monolith device to augment the removal of uraemic toxins during haemodialysis. J Mater Sci Mater Med. 25(6):1589-97