Angiopoietin-2 adsorption attempt with the cytokine adsorber cytosorb in critically ill patients

Abstract

Abstract Angiopoietin 2 (Ang-2) is a growth factor in angiogenesis, causing pericyte migration and vascular regression, leading to increased vascular permeability. Inflammatory mediators, hypoxia, hyperglycaemia and cancer stimulate its secretion. Particularly in sepsis, high Ang-2 levels appear to be a prognostic marker for morbidity and mortality in the critically ill. As an important trigger for endothelial damage one therapeutic option in these patients might be the removal of Ang-2. The Cyto-SOLVE trial included patients with septic shock or rhabdomyolsis treated with the adsorber Cytosorb (CS) (included in continuous kidney replacement therapy) for the removal of cytokines and myoglobin. Ang-2 was measured in the patient´s blood and pre- and post-CS at defined time points (ten minutes, one, three, six, and twelve hours after initiation). Ang-2 extracorporeal clearances (ml/min) were calculated with: $$\:\left(bloodflow*\left(1-hematocrit\right)\right)*\left(\frac{concentration\:\left(pre-post\right)}{concentration\:\left(pre\right)}\right).$$ U-Test was used to compare different subgroups. 26 patients were included (17 with rhabdomyolsis and 9 with septic shock, median Ang-2 concentration prior to CS-application: 21,653 pg/ml). We observed a low Ang-2 adsorption in the first hour of CS application, resulting in a median Ang-2 extracorporeal clearance of 8.2 ml/min and 1.7 ml/min after 10 min and 1 h, respectively. There was no significant change in Ang-2 plasma concentrations at any time point. No significant difference in Ang-2 levels was observed between patients with septic shock (median: 31,916 pg/ml) and rhabdomyolysis (median 18,379 pg/ml, p = 0.241). The Cytosorb adsorber does not decrease Ang-2 concentrations by adsorption. Therefore, Ang-2 can be considered a reliable biomarker for endothelial dysfunction even in the presence of Cytosorb therapy in critically ill patients. Further studies should be conducted to determine whether the removal of Ang-2 could be beneficial when utilizing an appropriate device.