Cellular interleukin-1 receptor antagonist production in patients receiving on-line haemodiafiltration therapy

Background. Repetitive exposure to cytokine-inducing substances (pyrogens) results in chronic inflammation, which may significantly contribute to some of the long-term complications in dialysis patients. On-line dialysis modalities, such as on-line haemodiafiltration (HDF), raise particular concerns because of the administration of infusate prepared from potentially contaminated dialysis fluid. Hence, great retention capability for pyrogens is of critical importance for the safe performance of on-line systems. Methods. The microbiological safety of a novel on-line system, ONLINEplus(R), was assessed in clinical practice in five centres for 3 months. Infusate and dialysis fluid were regularly monitored for microbial counts, endotoxins, and cytokine-inducing activity. Levels of interleukin-1 receptor antagonist (IL-1Ra) were determined in supernatants of whole blood incubated either under pyrogen-free conditions (spontaneous cytokine production) or following low-dose endotoxin exposure (LPS-stimulated cytokine production). Results. We railed to detect microorganisms or endotoxin contamination of infusate during the entire study period. Moreover, neither infusate nor dialysis fluid demonstrated cytokine-inducing activity. Intradialytic IL-1Ra induction was not detected, as there was no difference between pre- and post-session values for both spontaneous and LPS-stimulated IL-1Ra production (115 +/- 26 vs 119 +/- 27 and 2445 +/- 353 vs 2724 +/- 362 pg/10(6) white blood cells (WBC), respectively). Neither the number of immunocompetent cells nor their capacity to produce IL-1Ra declined during this period, indicating that cells were not significantly stimulated during treatment. Spontaneous and LPS-induced ex vivo IL-1Ra generation remained unchanged after 3 months of on-line HDF therapy as compared with the start of the study (71 +/- 30 pre- vs 48 +/- 14 post-study, and 2559 +/- 811 vs 2384 +/- 744 pg/10(6) WBC, respectively). Conclusions. The present on-line system performed safely from a microbiological view-point as both the dialysis fluid and infusate were consistently free of microorganisms. endotoxins, and cytokine-inducing substances. As a result, on-line HDF therapy had no effect upon the chronic inflammatory responses in end-stage renal disease patients.