P1110IN VITRO CYTOKINE REMOVAL - COMPARISM OF CONVENTIONAL HDF AND HDX (MIDDLE-CUT-OFF-DIALYZER, BAXTER THERANOVA)
Authors: Koball Sebastian , Koertge Andreas , Heskamp Benjamin , Frimmel Silvius , Hinz Michael , Mitzner Steffen 
Published: June 2020

Abstract

Background and Aims
The removal of inflammatory mediators and cytokines is of great importance in the treatment of patients with acute or chronic renal failure. In patients with acute renal failure and sepsis, an attempt is made to achieve removal through the use of high-volume treatments or adsorbers in order to achieve better circulatory stability. In chronic dialysis patients, this has so far not been sufficiently addressed, but is important for mortality and cardiovascular events (MIA syndrome). Some studies show a superiority of HDF over conventional HD. By using new MCO filters in HD mode such as the Baxter Theranova (HDx), an improvement of cytokine status seems to be possible in both areas (chronic and acute).
The effectiveness of MCO filters (HDx) compared to high flux hemodiafiltration in the removal of interleukins (interleukin 6, interleukin 10 and TNF (tumor necrosis factor) alpha will be assessed.

Method
The efficacy of HDx was compared with that of conventional high-flux dialysis filters (Fresenius FX80, HDF) in HDF mode. Based on real world conditions the ultrafiltration/substitution rate was set to 50 ml/min. (blood flow 200 ml/min., dialysate flow 500 ml/min.) No effective ultrafiltration was used. The measurements were performed in vitro in a 3l pool of fresh frozen plasma (citrate anticoagulated, with additional heparin during dialysis treatment). IL6 (24.5 kDa) IL10 (18.6 kDa, dimer)) and TNFalpha (17.4 kDa, trimer) were added to the plasma pool in concentrations of 1.5 μg/l each. This results in very high cytokine levels, as for example in severe sepsis. Samples were taken before and after the dialyzer for 180 minutes (after 5, 15, 30, 60, 120 and 180 minutes).For HDF the measured cytokine concentration was corrected for ultrafiltration rates. In addition to cytokines, albumin and total protein concentration were measured (ELISA Kit LEGEND MAX Human IL-6 / IL-10 / TNF-α; Biolegend and Cobas Mira Plus; Roche Kit LT-AB 0103 and LT-TP 0253). Every test was repeat 5 times.

Results
Theranova HDx showed higher removal rates of all tested cytokines over a period of 180 minutes. A comparison of the concentrations at the beginning and end of the measurements showed:
IL-6 reduction - HDx about 77% / HDF about 63%.
IL-10 reduction - HDx about 53% and HDF about 22%.
TNF-α Reduction - HDx about 26%; HDF about 18%
The concentration of albumin and total serum protein was not significant different during the treatments in both groups.

Conclusion
Hemodialysis therapy with Theranova HDx appears to be a superior or equal therapy option for the removal of cytokines. This opens up new treatment options for both acute renal failure and chronic dialysis patients, especially if citrate anticoagulation is necessary. The ultrafiltration rate in HDF was lower than recommended for high volume diafiltration,but as high as in our real world experience. Therefore the effect of HDF could be underestimated. Clinical studies with clinically relevant blood flow and ultrafiltration rates are still necessary.