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The biocompatibility of dialyzers may influence the inflammatory state of hemodialysis patients. This study compares the effect of a high-flux polynephron membrane with other high-flux membranes, helixone and polyamide, on some inflammation biomarkers based on the analysis of circulating mononuclear cells (MC).The study included 47 patients on hemodialysis with helixone and polyamide; 9 formed the control group, without changes in their dialyzers throughout the study, and 38 formed the intervention group, in which their dialyzers were replaced by polynephron. In both groups, blood samples were taken at the beginning of the study before and after hemodialysis session, and at the end of the study 4 months later. In each extraction, biochemical parameters were determined, and MC isolated using Ficoll gradient. Production of reactive oxygen species and the percentage of activated MC (CD14+CD16+) were measured by flow cytometry, and protein levels of heat-shock proteins (Hsp70/Hsp90) studied by Western blot.After 1 hemodialysis session with different membranes, no significant differences were observed in the different parameters considered. After 4 months of dialysis with polynephron, a significant reduction in the percentage of CD14+CD16+ and in the β2-microglobulin reduction ratio were found, with respect to helixone and polyamide, without changes in the other parameters analyzed.The use of polynephron for 4 months reduces the percentage of CD14+CD16+ compared to helixone and polyamide, suggesting a better profile regarding activation of the inflammatory response. These findings could be explained by a better biocompatibility or an increased reduction of medium-sized toxic molecules.