An adsorbent monolith device to augment the removal of uraemic toxins during haemodialysis

Abstract

Adsorbents designed with porosity which allows the removal of protein bound and high molecular weight uraemic toxins may improve the effectiveness of haemodialysis treatment of chronic kidney disease (CKD). A nanoporous activated carbon monolith prototype designed for direct blood contact was first assessed for its capacity to remove albumin bound marker toxins indoxyl sulphate (IS), p-cresyl sulphate (p-CS) and high molecular weight cytokine interleukin-6 in spiked healthy donor studies. Haemodialysis patient blood samples were then used to measure the presence of these markers in pre- and post-dialysis blood and their removal by adsorbent recirculation of post-dialysis blood samples. Nanopores (20-100 nm) were necessary for marker uraemic toxin removal during in vitro studies. Limited removal of IS and p-CS occurred during haemodialysis, whereas almost complete removal occurred following perfusion through the carbon monoliths suggesting a key role for such adsorbent therapies in CKD patient care.

Fig. 1

Characterisation of nanoporous monolith porosity was carried out using PoreMaster mercury intrusion porosimetry and Sigma field emission gun-scanning electron microscopy (FEG-SEM) a Quantachrome data reduction software was used to calculate a mercury pore size distribution plot showing nanoporous domains of 2–100 nm within the prototype carbon monoliths. The second peak is produced by interparticulate spaces which are 1–10 microns in diameter. b An SEM micrograph of a transverse section of the nanoporous activated carbon monolith showed internal nanoporous domains (magnification ×100,000)

Fig. 2

a IL-6, b indoxyl sulphate and c p-cresyl sulphate remaining following filtration of spiked fresh human blood through nanoporous monoliths, microporous monoliths and spiked and non-spiked controls (n = 3, mean ± s.e.m.). Filled star P < 0.01 for concentration of IL-6, IS, p-CS remaining following monolith filtration compared to the positive control of spiked blood circulated without a monolith at each time point

Fig. 3

The concentration of a indoxyl sulphate (IS) and b p-cresyl sulphate (p-CS) remaining in dialysis patient blood samples pre-dialysis, post-dialysis and then after 30, 60 and 90 min filtration through the nanoporous carbon monoliths (n = 7) or tubing only controls (n = 4).Monolith filtration was carried out on 20 ml blood samples taken from patients post-dialysis. ^# P > 0.01 for pre-dialysis versus post dialysis levels of IS and p-CS. Filled star P < 0.01 for pre-dialysis compared to post-monolith filtration levels of IS and P = 0.01 for pre-dialysis compared to post-monolith filtration levels of p-CS

Fig. 4

The concentration of fibrinogen measured in dialysis patient blood samples pre-dialysis, post-dialysis and after 30, 60 and 90 min filtration through the nanoporous carbon monoliths (n = 5) or controls (n = 4). P > 0.01 for monolith filtration versus control sample concentration of fibrinogen