Association of markers of endothelial dysregulation Ang1 and Ang2 with acute kidney injury in critically ill patients

Crit Care. 2016 Jul 3;20(1):207. doi: 10.1186/s13054-016-1385-3.


Background: The role of endothelial dysregulation with acute kidney injury (AKI) in critically ill patients is unclear.

Methods: We retrospectively assessed the associations of AKI with biomarkers of endothelial function and inflammation among 948 subjects admitted to the intensive care unit (ICU) at Harborview Medical Center (Seattle, WA, USA). From plasma obtained within 24 h of enrollment, we measured angiopoietin (Ang)-1 and Ang-2 alongside biomarkers of inflammation, including interleukin (IL)-6, IL-17 and granulocyte colony-stimulating factor. We tested for associations between standardized concentrations of biomarkers and AKI, defined by serum creatinine, from ICU admission to up to 7 days later.

Results: All biomarkers of inflammation and endothelial dysfunction were associated with AKI. After adjustment for demographics, comorbidities, and IL-6 concentration, every standard deviation of Ang-1 concentration was associated with a 19 % lower risk of AKI (relative risk (RR) = 0.85, 95 % confidence interval (CI) 0.77-0.93, p < 0.001). Conversely, higher Ang-2 concentration was associated with higher risk of AKI (RR per standard deviation = 1.17, 95 % CI 1.13-1.22, p < 0.001).

Conclusions: In critically ill patients, plasma concentration of the endothelial growth factors Ang-1 and Ang-2 are associated with AKI, independently of inflammation.

Keywords: Acute kidney injury; Endothelial dysfunction; Endothelial dysregulation; Sepsis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / physiopathology*
  • Adult
  • Aged
  • Angiopoietin-1 / analysis*
  • Angiopoietin-1 / blood
  • Angiopoietin-2 / analysis*
  • Angiopoietin-2 / blood
  • Biomarkers / analysis
  • Biomarkers / blood
  • Cohort Studies
  • Critical Illness / mortality
  • Female
  • Humans
  • Intensive Care Units / organization & administration
  • Intensive Care Units / statistics & numerical data
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Retrospective Studies
  • Washington


  • ANGPT1 protein, human
  • ANGPT2 protein, human
  • Angiopoietin-1
  • Angiopoietin-2
  • Biomarkers
  • IL6 protein, human
  • Interleukin-6