Association of the soluble form of the endothelial Tie2 receptor with organ failure and mortality in patients with sepsis and ARDS

Science and Research

INTRODUCTION: Tie2 is an endothelial surface receptor critically involved in angiogenesis, cell-integrity, and survival. During inflammatory disorders such as sepsis and ARDS, the receptor is shed from the endothelial surface, contributing to a reduction of its protective downstream signaling ultimately contributing to endothelial permeability and thereby capillary leakage. This study investigates the association of the soluble form of Tie2 (sTie2), with multiorgan failure, requirement of dialysis and mortality. METHODOLOGY: We conducted a biomarker study using serum samples from sepsis and/or ARDS patients admitted to the medical intensive care unit (ICU) of Hannover Medical School. sTie2 was quantified by Multiplex Luminex Assay in serum samples collected on the day of ICU admission. Correlations between sTie2 levels and baseline SOFA-score, duration of vasopressor therapy, and duration of mechanical ventilation were evaluated using Pearson's correlation coefficient. The Wilcoxon rank-sum test was employed to compare sTie2 levels between individuals with and without renal replacement therapy, as well as between survivors and non-survivors. Cox regression models were applied to assess the independent association of sTie2 with 28-day mortality. RESULTS: sTie2 levels showed an inverse correlation with the SOFA-score (R = -0.2, p = 0.003) and were lower in patients requiring renal replacement therapy (17.4 [12.25-22.48] vs. 21.35 [14.91-29.08] ng/ml, p = 0.003) and in non-survivors (14.54 [10.96-15.02] vs. 21.01 [15-28.12] ng/ml, p < 0.001). No correlation was found between sTie2 and the number of days requiring vasopressor therapy or mechanical ventilation. Using multivariable cox regression, sTie2 was independently associated with mortality at 28-days (sTie2, log(ng/ml) - HR 0.35, 95% CI 0.21-0.57, p < 0.001). CONCLUSION: In this study of severely ill ICU patients, sTie2 was inversely related to severity of disease and to outcome. If the decrease in sTie2 is adaptive or maladaptive remains unclear but future investigations are required analysing the exact pathophysiological role of sTie2 to evaluate the biomarker as a potential target for the treatment of capillary leakage in patients with sepsis and/or ARDS.