Cytokine Induction in Patients Undergoing Regular Online Hemodiafiltration Treatment

Abstract

End-stage renal disease (ESRD) patients are known to suffer from chronic inflammation as the result of an ongoing subacute cytokine induction, which may contribute considerably to dialysis-related, long-term morbidity and mortality. Preparation of infusate from cytokine-inducing dialysis fluid and its administration in large quantities as well as the use of high-flux membranes bear the risk of aggravating the chronic inflammatory response among online hemodiafiltration (online HDF) patients. In order to assess the inflammatory risk associated with online HDF, we compared the cytokine induction profile of ESRD patients receiving either online HDF or low-flux hemodialysis (low-flux HD). Specifically, we measured spontaneous and lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNFalpha) and interleukin-1 receptor antagonist (IL-1Ra) release during ex vivo incubation of whole blood. Ultrapure dialysis fluid and polysulfone membranes were used for both treatment modalities. LPS-stimulated release of TNFalpha and IL-1Ra was elevated for both online HDF and low-flux HD patients compared to healthy individuals (TNFalpha: 2,336 +/- 346 and 2,192 +/- 398 versus 1,218 +/- 224 pg/106 white blood cells [WBC]; IL-1Ra: 2,410 +/- 284 and 2,326 +/- 186 versus 1,678 +/- 219 pg/106 WBC). Likewise, spontaneous production of TNFalpha, but not IL-1Ra, was higher in online HDF and low-flux HD patients than in normal controls (37 +/- 32 and 22 +/- 19 versus 0.8 +/- 0.3 pg TNFalpha/106 WBC). There was no difference in spontaneous and LPS-stimulated cytokine release between both dialysis groups. In addition, intradialytic cytokine induction was not significant for either treatment modality as spontaneous and LPS-stimulated cytokine release were not increased postdialysis. These findings indicate that online HDF does not contribute to chronic leukocyte activation and, consequently, does not place ESRD patients at greater risk with respect to inflammatory morbidity and mortality.

Continuous Veno-Venous High Cut-Off Hemodialysis Compared to Continuous Veno-Venous Hemodiafiltration in Intensive Care Unit Acute Kidney Injury Patients

“…Basal and after PMA stimulation production rate of superoxide anion by leukocytes at the beginning and at the end of each session was not significantly different with the 2 modalities. Cytokine induction has also been considered the trigger of the inflammatory response and a critical parameter of dialysis biocompatibility during RRT [37] and high levels of pro-inflammatory cytokines have been associated with increased mortality in AKI [38,39]. We found that both pro-and anti-inflammatory cytokines plasma levels did not increase after HCO HD, suggesting that it might not alter the balance of cytokines production.…”

On‐line Hemodiafiltration Does Not Induce Inflammatory Response in End‐stage Renal Disease Patients: Results From a Multicenter Cross‐over Study

“…However, there is no evidence up to now that pyrogenic reactions occur more frequently during on‐line convective therapies than during low‐flux HD (23,24). Subclinically, no difference between on‐line HDF and conventional HD has been observed, as chronic inflammation was not altered by on‐line HDF and there was no induction of cytokines during the session (25,26).…”

Online Hemodiafiltration

“…Weber and coworkers could not demonstrate an increase in pro‐inflammatory cytokines or markers of monocyte activation after a 3‐month period of online HDF (11). Others reported a decrease of pro‐inflammatory cytokines (interleukin 6 [IL‐6] and tumor necrosis‐factor α[TNFα]) after switching to online HDF (12) or confirmed the absence of significant leukocyte activation (as measured by TNF‐α and IL‐1 receptor antagonist concentration) in online HDF, with similar results as in low‐flux hemodialysis (13). It is conceivable that different adsorptive properties and biocompatibility of dialysis membranes should be kept in mind when interpreting these results.…”