In Vitro Assessment of Dialysis Membrane as an Endotoxin Transfer Barrier: Geometry, Morphology, and Permeability

Abstract

High-flux dialysis membranes used with bicarbonate dialysis fluid increase the risk of back diffusion of bacterial endotoxin into the blood during hemodialysis. Endotoxin transfer of various synthetic fiber membranes was tested with bacterial culture filtrates using an in vitro system testing both diffusive and convective conditions. Membranes were tested in a simulated dialysis mode with endotoxin challenge material (approximately 420 EU/mL) added to the dialysis fluid, with saline used to model both blood and dialysis fluid. Samples were taken of both blood and dialysis fluid, and analyzed using a kinetic turbidimetric Limulus amoebocyte lysate assay. Endotoxin was found in all of the blood circuit samples, except for the Fresenius Optiflux F200NR(e) and thick-wall membranes. All membranes tested removed approximately 95% of the endotoxin from solution, with the residual approximately 5% recirculating within the dialysis fluid compartment. Endotoxin distribution through the fiber membrane was examined using a fluorescent-labeled endotoxin conjugate. Fluorescence images indicate that adsorption occurs throughout the membrane wall, with the greatest concentration of endotoxin located at the inner lumen. Contact angle analysis was able to show that all membranes exhibit a more hydrophilic lumen and a more hydrophobic outer surface except for the polyethersulfone membranes, which were of equal hydrophobicity. Resulting data indicate that fiber geometry plays an important role in the ability of the membrane to inhibit endotoxin transfer, and that both adsorption and filtration are methods by which endotoxin is retained and removed from the dialysis fluid circuit.

Endotoxemia after high cutoff hemodialysis for treatment of patient with multiple myeloma can be prevented by using ultrapure dialysate: A case report

“…[20][21][22][23][24] But still, the concerns about endotoxins in HD progressively increase in recent years [25][26][27][28][29][30] and ultrapure dialysate is proposed to be used in HD. The endotoxins in standard dialysate, usually below 2 EU/mL as required, may enter blood by back ultrafiltration or back diffusion.…”

“…This possibility is usually negligible for traditional HD because the cutoff effect, adsorption function of outer surface by the traditional filter, as well as a high transmembrane pressure (TMP) commonly required in HD for ultrafiltration, may prevent endotoxins from entering blood. [20][21][22][23][24] But still, the concerns about endotoxins in HD progressively increase in recent years [25][26][27][28][29][30] and ultrapure dialysate is proposed to be used in HD. 31,32 For HCO-HD, using a filter with large pore size and duration extended to 8 hours may be in favor for endotoxins entering blood due to high cutoff effect and low TMP required for ultrafiltration.…”

The Effect of Intra-Dialytic Exercise on Inflammation and Blood Endotoxin Levels

“…1). Since endotoxins and cytokines can be adsorbed by dialysis membranes [18,19] and there may be enhanced clearance due to convection with haemodiafiltration [20] and smaller endotoxins (10-20 kDa), BG, D-lactate may also be removed during dialysis, additional blood samples were taken 1-3 h post dialysis to look for a potential rebound rise in any of these parameters caused by either intra-dialytic exercise or the HD procedure. Such rebound would be anticipated if endotoxin and inflammatory cytokine were generated by the dialysis procedure.…”

Hemodialysis membrane surface chemistry as a barrier to lipopolysaccharide transfer

“…Blood is passed through the fiber lumen while dialysate is circulated in a tangential flow outside of the fiber bundles. As blood toxins diffuse into the dialysate it is also possible for any impurities in the dialysate to enter the blood through back‐filtration—this is of particular concern for dialysate contaminated with bacterial endotoxin, or lipopolysaccharide (LPS) . Use of high‐flux dialyzers, which remove large percentages of middle molecular weight toxins such as β 2 ‐microglobulin (MW 11 kDa), further raises the potential of back‐filtration of LPS in contaminated dialysate …”

“…Several materials and membrane chemical compositions have been studied for their ability to limit LPS back filtration either in preultrafiltration stages or directly during dialysis treatment. Among these are: polysulfone (PS), polyamide, cellulosic tri‐acetate, ceramic, and polyester . Reduced back‐filtration has been ascribed primarily to LPS adsorption, with filtration also playing a significant role .…”