Reduced Cytokine Induction and Removal of Complement Products with Synthetic Hemodialysis Membranes

Abstract

The increasing use of high-flux membranes for hemodialysis (HD) has raised concerns that these membranes may confer a higher risk of exposure to cytokine-inducing, bacterial substances (CIS) in the dialysate. Several studies, however, reported higher transfer of CIS through low-flux cellulosic than high-flux synthetic membranes. This surprising paradox was explained by adsorption of CIS to certain high-flux membranes. In order to investigate flux and membrane type independently, we studied two synthetic Polyflux (PF) membranes of the same type but with different flux properties and compared them to a cellulosic membrane (Cuprophan). Three different approaches were employed: (1) cytokine induction in whole blood during in vitro HD contaminated with bacterial filtrates, (2) removal of recombinant C5a, and (3) transfer of purified lipopolysaccharide (LPS). After 90 min recirculation of whole blood, the appearance of IL-6-inducing substances on the blood side was lowest with high-flux PF (1.1 ± 0.2 ng/ml), slightly higher with low-flux PF (1.9 ± 0.7 ng/ml) and highest with Cuprophan (4.1 ± 1 ng/ml). Recombinant C5a added to plasma on the blood side was markedly removed by high-flux PF (by 83%), to a lesser degree and only in the presence of ultrafiltration with low-flux PF (by 54%) and not significantly with Cuprophan (by 11%). Significant transfer of purified LPS from the dialysate onto the blood side was only observed with the cellulosic membrane. We conclude that in contrast to cellulosic membranes, certain synthetic membranes do not permit transfer of LPS. Cytokine induction on the blood side is further reduced by the use of high-flux membranes due to removal of activated complement factors.

Treatment of severe lactic acidosis during the pre-anhepatic stage of liver transplant surgery with intraoperative hemodialysis

“…Hence, intraoperative dialysis has become our standard of care during liver transplant surgery for patients who require dialysis preoperatively to manage both volume and acidosis. At our institution, hemodialysis is performed with biocompatible membranes, which theoretically reduce protein oxidation and complement activation, thereby providing a more stable procedure [47][48][49]. Dialysis membranes effectively remove molecules below a molecular weight of 1,500 Da.…”

The Place of Large Pore Membranes in the Treatment Portfolio of Patients on Hemodialysis

“…Until recently, the transfer of bacterial contamination products through MCO and HCO membranes was only evaluated in closed in vitro dialysis cir-cuits [28][29][30][31][32] . Using such in vitro investigations, it could be demonstrated that increasing pore size does not result in higher cross-contamination towards the blood side of lipopolysaccharide (LPS) isolated from Escherichia coli O55:B5 [33] .…”

Leukocyte Function in High-Flux Hemodialysis

“…Another aspect is the removal of cytokines and other inflammatory markers (lipopolysaccharide fragments, granulocyte inhibitory proteins 1 and 2, IL-1, TNF-) and complement factors (C3a, C5a) by the hemodialysis procedure as well as the adsorption of substances to the hydrophobic high-flux membrane (e.g. factor D) (Clark et al 1999;Schindler et al 2006). Dialysis can reduce leukocyte-endothelial interactions and impair transmigration (Thylen et al 1997).…”

“…In patients on hemodialysis with cuprophane or polysulfone membranes, a significantly higher serum level of MCP-1 is seen compared with healthy subjects both before and after the hemodialysis session, independent of the membrane used (Jacobson et al 2000;Thylen et al 2000). Biocompatibility of dialysis membranes probably plays an important role in determining leukocyte function in patients on hemodialysis (Himmelfarb et al 1991;Himmelfarb et al 1993;Hernandez et al 2004;Schindler et al 2006). High serum levels of cytokines and chemokines have been observed in patients on hemodialysis with modified cellulose membranes (Descamps-Latscha 1993; Pawlak et al 2004;Muniz-Junqueira et al 2005).…”

“…High serum levels of cytokines and chemokines have been observed in patients on hemodialysis with modified cellulose membranes (Descamps-Latscha 1993; Pawlak et al 2004;Muniz-Junqueira et al 2005). Highflux hemodialysis causes lower levels of IL-6 and IL-1 than low-flux hemodialysis or dialysis with cuprophane membranes (Schindler et al 2006). Our group has previously demonstrated that neutrophils and monocytes recruited to an induced interstitial inflammatory site in patients treated with low-flux bioincompatible hemodialysis have an impaired capacity of mobilizing CD11b in response to the induced inflammation, compared with the corresponding cells from healthy subjects Jacobson et al 2002).…”