On-line Production of Ultrapure Substitution Fluid Reduces TNF-alpha- and IL-6 Release in Patients on Hemodiafiltration Therapy

Abstract

On-line hemodiafiltration (HDF) has been introduced into clinical practice in the last few years. The most important technical and regulatory challenges were the safety and microbiological quality of ultrafiltrated substitution/replacement fluid. The application of ultrafilters in a different technical arrangement in the fluid path based on polysulfone or polyamide membranes should prevent patient contact with endotoxins and other pyrogenic or bacteria-derived substances. After resolving these problems and providing clinically safe and technically robust product solutions, increasing numbers of patients have been treated, especially those with severe clinical conditions, e.g., diabetes, hypo- or hypertension. The benefit for patients was brought about by the increase of substitution rate in hemodiafiltration and enhancing convective mass transfer. The impact of highly convective therapy modes on the state of immunomodulation towards the syndrome of microinflammation has not been investigated in a systematic prospective manner. In this study, 8 patients undergoing bag-HDF treatment with lactate buffered solution were investigated before online HDF treatment with commercially available whole blood stimulation assays testing for TNF-alpha and IL-6 release. Both assays are based on phytohemagglutinine (for TNF) and lipo-polysaccharide stimulation (for IL-6). Thereafter the patients were switched to on-line production of substitution fluid. After a wash-out period of 2 sessions the whole blood stimulation assays were applied to the same patients. The Wilcoxon test (for paired analysis) was done, revealing a statistically significant lower release of proinflammtory cytokines from patients' blood upon stimulation with PHA or LPS. The reduction of IL-6 and TNF concentration and release capacity in whole blood may be attributed to the use of high quality ultrapure substitution fluid and dialysate in on-line treatment instead of lactate buffer bag solution. These results indicate that not only an increase of convective mass tranfer by higher volume exchange, but also a decrease in unspecific activation of immunocompetent cells may have advantages for HDF-treated patients.