A haemocompatible and scalable nanoporous adsorbent monolith synthesised using a novel lignin binder route to augment the adsorption of poorly removed uraemic toxins in haemodialysis

摘要

Nanoporous adsorbents are promising materials to augment the efficacy of haemodialysis for the treatment of end stage renal disease where mortality rates remain unacceptably high despite improvements in membrane technology. Complications are linked in part to inefficient removal of protein bound and high molecular weight uremic toxins including key marker molecules albumin bound indoxyl sulphate (IS) and p-cresyl sulphate (PCS) and large inflammatory cytokines such as IL-6. The following study describes the assessment of a nanoporous activated carbon monolith produced using a novel binder synthesis route for scale up as an in line device to augment haemodialysis through adsorption of these toxins. Small and large monoliths were synthesised using an optimised ratio of lignin binder to porous resin of 1 in 4. Small monoliths showing combined significant IS, p-CS and IL-6 adsorption were used to measure haemocompatibility in an ex vivo healthy donor blood perfusion model, assessing coagulation, platelet, granulocyte, t cell and complement activation, haemolysis, adsorption of electrolytes and plasma proteins. The small monoliths were tested in a niave rat model and showed stable blood gas values, blood pressure, blood biochemistry and the absence of coagulopathies. These monoliths were scaled up to a clinically relevant size and were able to maintain adsorption of protein bound uremic toxins IS, PCS and high molecular weight cytokines TNF and IL-6 over 60 minutes using a flow rate of 300 mL/min without platelet activation. The nanoporous monoliths where haemocompatible and retained adsorptive efficacy on scale up with negligible pressure drop across the system indicating potential for use as an in-line device to improve haemodialysis efficacy by adsorption of otherwise poorly removed uraemic toxins.