In vitro assessment of mixed matrix hemodialysis membrane for achieving endotoxin-free dialysate combined with high removal of uremic toxins from human plasma

Abstract

For a single hemodialysis session nearly 500 L of water are consumed for obtaining pyrogen-free dialysis fluid. However, many efforts are required to avoid biofilm formation in the system and risk of contamination can persist. Water scarcity and inadequate water purification facilities worsen contamination risk in developing countries. Here, we investigated the application of an activated carbon (AC)/polyethersulfone/polyvinylpyrrolidone mixed matrix membrane (MMM) for achieving for the first time endotoxin-free dialysate and high removal of uremic toxins from human plasma with a single membrane. The MMM, thanks to sorbent AC, can remove approximately 10 times more endotoxins from dialysis fluid compared to commercial fibers. Pyrogens transport through the MMM was investigated analyzing inflammation in THP-1 monocytes incubated with samples from the dialysis circuit, revealing safety-barrier properties of the MMM. Importantly, endotoxins from dialysate and protein-bound toxins from human plasma can be removed simultaneously without compromising AC adsorption capacity. We estimated that only 0.15 m2 of MMM is needed to totally remove the daily production of the protein-bound toxins indoxyl sulfate and hippuric acid and to completely remove endotoxins in a wearable artificial kidney (WAK) device. Our results could open up new possibilities for dialysis therapy with low water consumption including WAK and where purity and scarcity of water are limiting factors for hemodialysis treatment. Statement of SignificanceHemodialysis is a life-sustaining extracorporeal treatment for renal disease, however the production of pyrogen-free dialysate is very costly and water demanding. Biofilm formation in the system worsens bacteria contamination risk. Pyrogens could be transferred into the patients’ blood and trigger inflammation. Here, we show for the first time that a mixed matrix membrane composed of polyethersulfone/polyvinylpyrrolidone and activated carbon can achieve simultaneous complete removal of endotoxins from dialysate and high removal of uremic toxins from human plasma without compromising activated carbon adsorption capacity. The mixed matrix membrane could find future applications for simultaneous blood purification and dialysate depyrogenation thus lowering water consumption as for wearable artificial kidney devices and where purity and scarcity of water hamper hemodialysis treatment.