Endotoxin-binding affinity of sevelamer: a potential novel anti-inflammatory mechanism  Phyllis P. Sun, Mary C. Perianayagam, Bertrand L. Jaber  Kidney International  Volume 76, Pages S20-S25 (December 2009) DOI: 10.1038/ki.2009.403 Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 1 Dose-dependent effect of sevelamer hydrochloride on free endotoxin levels. Sevelamer hydrochloride (0–50 mg/ml) was incubated with purified Escherichia coli endotoxin (10 ng/ml) for 1 h, and supernatants were then assayed for endotoxin. P<0.001 by Friedman's test for overall difference between concentrations. *P=0.03 versus control (at 1 h) by Wilcoxon signed-rank test. Reproduced from Perianayagam and Jaber57 with permission from S Karger AG, Basel. Kidney International 2009 76, S20-S25DOI: (10.1038/ki.2009.403) Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 2 Dose-dependent effect of sevelamer hydrochloride on tumor necrosis factor-α (TNF-α) production levels. THP-1-derived monocytes were incubated with or without supernatants obtained from the mixture of sevelamer hydrochloride (0–50 mg/ml) and purified Escherichia coli endotoxin (10 ng/ml) for 24 h. Cell supernatants were then assayed for TNF-α. P<0.001 by Friedman's test for overall difference between concentrations. *P=0.03 versus control (at 24 h) by Wilcoxon signed-rank test. Reproduced from Perianayagam and Jaber57 with permission from S Karger AG, Basel. Kidney International 2009 76, S20-S25DOI: (10.1038/ki.2009.403) Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 3 Plasma endotoxin levels in patients on maintenance hemodialysis, stratified by sevelamer hydrochloride use. *P=0.001 versus non-sevelamer by Mann-Whitney test. Reproduced with permission from Sun et al.58 Kidney International 2009 76, S20-S25DOI: (10.1038/ki.2009.403) Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 4 Proposed enterohepatic cycle of bacterial lipolysaccharide (LPS) and hypothesized intestinal binding by sevelamer. Gut-derived LPS enters the bloodstream through the portal circulation or the lymphatic system. Circulating chylomicrons shuttle LPS back to the liver, where it is dumped into the biliary tract and subsequently excreted in the bile. In the biliary tract, LPS might bind to bile acids forming a complex, which in turn could bind sevelamer in the intestinal tract, thus preventing LPS translocation into the circulation. Kidney International 2009 76, S20-S25DOI: (10.1038/ki.2009.403) Copyright © 2009 International Society of Nephrology Terms and Conditions