A switch to high-flux helixone membranes reverses suppressed interferon-gamma production in patients on low-flux dialysis

Abstract

Long-term hemodialysis (HD) induces an inflammatory response and is associated with a suppressed cellular immune response manifested, in part, by impaired interferon (IFN-gamma) production. We investigated the effect of high-flux HD using the synthetic Helixone membrane and ultrafiltered dialysate on plasma levels of inflammatory mediators and on the whole blood production of IFN-gamma.

Methods: Twelve ESRD patients were dialyzed under low-flux HD (polysulfone F6) and again after 6 weeks of high-flux HD (Helixone FX100). Ultrafiltered bicarbonate dialysate without bacterial growth and no detectable endotoxin was used throughout the study. Plasma levels of urea, albumin, beta(2)-microglobulin (beta(2)-m), interleukin (IL)-6, C-reactive protein (CRP), IL-1 receptor antagonist (IL-1Ra), IL-18, and IL-18-binding protein (IL-18BP) were measured. In addition, the Staphylococcus epidermidis-induced production of IFN-gamma and IL-18 was assessed in whole blood cultures of HD patients as well as in 9 healthy subjects.

Results: Plasma levels of urea, albumin, IL-6, IL-1Ra and CRP were not significantly different between high-flux and low-flux HD. In contrast, beta(2)-m levels decreased significantly by 31% with high-flux Helixone (p < 0.002). Stimulated whole blood production of IFN-gamma was reduced in low-flux HD but increased to near normal levels after 6 weeks of high-flux HD. Plasma levels of free IL-18 and its specific inhibitor IL-18BP were not different between the two dialyzer membranes.

Conclusion: Compared to low-flux polysulfone HD with ultrafiltered dialysate, high-flux HD with the synthetic Helixone membrane did not result in a significant change in plasma levels of proinflammatory (IL-6, CRP, IL-18) and anti-inflammatory (IL-1Ra, IL-18BP) cytokines. However, high-flux HD restores whole blood IFN-gamma production without significant changes in free IL-18. Therefore, the immune modulation in high-flux HD is likely due to removal of inhibitors of IFN-gamma production other than IL-18BP.