Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK Study

Introduction: Angiopoietin II (Ang-II) plays a pivotal role in the development of microcirculatory dysfunction as it provokes endothelial barrier disruption in patients with sepsis or septic shock. In particular, those with acute kidney injury show high Ang-II concentrations. So far, it is unclear w...

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Main Authors: Veronika Bucher, Helen Graf, Johannes Zander, Uwe Liebchen, Danilo Hackner, Caroline Gräfe, Martin Bender, Michael Zoller, Christina Scharf
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/11/2436
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author Veronika Bucher
Helen Graf
Johannes Zander
Uwe Liebchen
Danilo Hackner
Caroline Gräfe
Martin Bender
Michael Zoller
Christina Scharf
author_facet Veronika Bucher
Helen Graf
Johannes Zander
Uwe Liebchen
Danilo Hackner
Caroline Gräfe
Martin Bender
Michael Zoller
Christina Scharf
author_sort Veronika Bucher
collection DOAJ
description Introduction: Angiopoietin II (Ang-II) plays a pivotal role in the development of microcirculatory dysfunction as it provokes endothelial barrier disruption in patients with sepsis or septic shock. In particular, those with acute kidney injury show high Ang-II concentrations. So far, it is unclear which covariates influence Ang-II concentration in the early phase of sepsis, especially if extracorporeal therapies also do. Methods: Ang-II concentrations were measured in 171 patients with sepsis after the first day of antibiotic treatment between 03/2013 and 01/2015. Ang-II was correlated with potential influencing factors (Spearman correlation). A multivariate model was established including the significant correlating parameters. The Mann–Whitney U test and the Kruskal–Wallis test were used to detect significant differences in Ang-II concentration. Results: The median Ang-II concentration was 8015 pg/mL (interquartile range (IQR): 5024–14,185). A total of forty patients were treated with kidney replacement therapy (KRT) and 20 were supported by venovenous extracorporeal membrane oxygenation (vv-ECMO). Sequential organ failure assessment (SOFA) score (r = 0.541), creatinine clearance (r = −0.467), urinary output (r = −0.289), interleukin (IL)-6 (r = 0.529), C-reactive protein (CRP) (r = 0.241), platelet count (r = −0.419), bilirubin (r = 0.565), lactate (r = 0.322), KRT (r = 0.451), and fluid balance (r = 0.373) significantly correlated with Ang-II concentration and were included in the multivariate model. There, creatinine clearance (<i>p</i> < 0.01, b = −26.3, 95% confidence interval (CI) −41.8–−10.8), fluid balance (<i>p</i> = 0.002, b = 0.92, 95% CI 0.33–1.51), and CRP (<i>p</i> = 0.004, b = 127.6, 95% CI 41.6–213.7) were associated with Ang-II concentration. Furthermore, patients with KRT (median: 15,219 pg/mL, IQR: 10,548–20,270) had significantly (<i>p</i> < 0.01) higher Ang-II concentrations than those with vv-ECMO support (median: 6412 pg/mL, IQR: 5246–10,257) or those without extracorporeal therapy (median: 7156 pg/mL, IQR: 4409–12,741). Conclusion: Increased CRP, positive fluid balance, and impaired kidney function were associated with higher Ang-II concentrations in critically ill patients in the early stage of sepsis in this post hoc analysis. In particular, patients with KRT had very high Ang-II concentrations, whereas the use of vv-ECMO was not related to higher Ang-II concentrations. The significance for clinical practice should be clarified by a prospective study with standardized measurements.
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spelling doaj-art-1831d90b999d42adb3e83e41fa7f8fa62024-11-26T17:52:42ZengMDPI AGBiomedicines2227-90592024-10-011211243610.3390/biomedicines12112436Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK StudyVeronika Bucher0Helen Graf1Johannes Zander2Uwe Liebchen3Danilo Hackner4Caroline Gräfe5Martin Bender6Michael Zoller7Christina Scharf8Department of Anaesthesiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377 Munich, GermanyDepartment of Anaesthesiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377 Munich, GermanyLabor Dr. Brunner, 78464 Konstanz, GermanyDepartment of Anaesthesiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377 Munich, GermanyDepartment of Anaesthesiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377 Munich, GermanyDepartment of Anaesthesiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377 Munich, GermanyDepartment of Anaesthesiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377 Munich, GermanyDepartment of Anaesthesiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377 Munich, GermanyDepartment of Anaesthesiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377 Munich, GermanyIntroduction: Angiopoietin II (Ang-II) plays a pivotal role in the development of microcirculatory dysfunction as it provokes endothelial barrier disruption in patients with sepsis or septic shock. In particular, those with acute kidney injury show high Ang-II concentrations. So far, it is unclear which covariates influence Ang-II concentration in the early phase of sepsis, especially if extracorporeal therapies also do. Methods: Ang-II concentrations were measured in 171 patients with sepsis after the first day of antibiotic treatment between 03/2013 and 01/2015. Ang-II was correlated with potential influencing factors (Spearman correlation). A multivariate model was established including the significant correlating parameters. The Mann–Whitney U test and the Kruskal–Wallis test were used to detect significant differences in Ang-II concentration. Results: The median Ang-II concentration was 8015 pg/mL (interquartile range (IQR): 5024–14,185). A total of forty patients were treated with kidney replacement therapy (KRT) and 20 were supported by venovenous extracorporeal membrane oxygenation (vv-ECMO). Sequential organ failure assessment (SOFA) score (r = 0.541), creatinine clearance (r = −0.467), urinary output (r = −0.289), interleukin (IL)-6 (r = 0.529), C-reactive protein (CRP) (r = 0.241), platelet count (r = −0.419), bilirubin (r = 0.565), lactate (r = 0.322), KRT (r = 0.451), and fluid balance (r = 0.373) significantly correlated with Ang-II concentration and were included in the multivariate model. There, creatinine clearance (<i>p</i> < 0.01, b = −26.3, 95% confidence interval (CI) −41.8–−10.8), fluid balance (<i>p</i> = 0.002, b = 0.92, 95% CI 0.33–1.51), and CRP (<i>p</i> = 0.004, b = 127.6, 95% CI 41.6–213.7) were associated with Ang-II concentration. Furthermore, patients with KRT (median: 15,219 pg/mL, IQR: 10,548–20,270) had significantly (<i>p</i> < 0.01) higher Ang-II concentrations than those with vv-ECMO support (median: 6412 pg/mL, IQR: 5246–10,257) or those without extracorporeal therapy (median: 7156 pg/mL, IQR: 4409–12,741). Conclusion: Increased CRP, positive fluid balance, and impaired kidney function were associated with higher Ang-II concentrations in critically ill patients in the early stage of sepsis in this post hoc analysis. In particular, patients with KRT had very high Ang-II concentrations, whereas the use of vv-ECMO was not related to higher Ang-II concentrations. The significance for clinical practice should be clarified by a prospective study with standardized measurements.https://www.mdpi.com/2227-9059/12/11/2436angiopoietin-2sepsiskidney replacement therapy (KRT)extracorporeal membrane oxygenation (ECMO)fluid balancecreatinine clearance
spellingShingle Veronika Bucher
Helen Graf
Johannes Zander
Uwe Liebchen
Danilo Hackner
Caroline Gräfe
Martin Bender
Michael Zoller
Christina Scharf
Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK Study
Biomedicines
angiopoietin-2
sepsis
kidney replacement therapy (KRT)
extracorporeal membrane oxygenation (ECMO)
fluid balance
creatinine clearance
title Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK Study
title_full Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK Study
title_fullStr Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK Study
title_full_unstemmed Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK Study
title_short Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK Study
title_sort angiopoietin ii in critically ill septic patients a post hoc analysis of the drak study
topic angiopoietin-2
sepsis
kidney replacement therapy (KRT)
extracorporeal membrane oxygenation (ECMO)
fluid balance
creatinine clearance
url https://www.mdpi.com/2227-9059/12/11/2436
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