Angiopoietin 2 Levels Are Associated With the Development and Trajectory of Sepsis-Associated AKI

Sunday, February 23, 2025

9:45am – 10:45am Eastern Time

Location: Connections Central Theater 1

Syed Arsalan Zaidi, MD., MS.

UPMC Presbyterian

Disclosure(s): No relevant financial relationship(s) to disclose.
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Xinlei Chen, MS

Data scientist
University of Pittsburgh

Disclosure information not submitted.
David T. Huang, MD, MPH

Professor of Critical Care Medicine, Emergency Medicine, and Clinical and Translational Science
UPMC

Disclosure information not submitted.
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Donald M. Yealy, MD.

SVP @ UPMC & Chief Medical Officer
UPMC

Disclosure information not submitted.
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Derek C. Angus, MD, MPH

Professor of Medicine, Professor of Health Policy and Management,
UPMC

Disclosure information not submitted.
Nathan Shapiro, M.D.

Professor of Emergency Medicine
Beth Israel Deaconess Medical Center

Disclosure information not submitted.
Hernando Gomez, MD, MPH

Associate Professor of Critical Care Medicine
University of Pittsburgh

Disclosure information not submitted.

Disclosure(s):

Syed Arsalan Zaidi, MD., MS.: No relevant financial relationship(s) to disclose.

Introduction: Endothelial dysfunction (ED) is a key potential mechanism of end-organ injury in sepsis-associated acute kidney injury (SA-AKI). Little is known about specific mechanisms leading to endothelial injury and activation. We sought to describe the role of the Angiopoietin 2 (ANG2)/TIE2 pathway, a potential effector of ED, in the development of sepsis-associated AKI.

Methods: We analyzed prospectively collected data from the ProCESS sepsis resuscitation trial, which enrolled more than 1300 adults with septic shock. Plasma endothelial dysfunction and injury biomarkers, including ANG2, measured at study enrollment (0 h) and 6 h, 24 h, and 72 h, were linked to the development of moderate-severe AKI, defined as KDIGO AKI stage 2 or 3 within the first 3 days after enrollment, and all-cause / all-location 30 d mortality using logistic regression models. We adjusted for age, gender, CKD, CLD, use of vasopressors in the first 24 hours, Charlson comorbidity index, and Baseline APACHE score. Descriptive analysis results are reported as mean +/- standard deviation.

Results: Among 842 septic shock patients with available biomarker data, 157 (18.6%) developed stage 2/3 AKI. Enrollment plasma levels of ANG2 were higher in those who developed stage 2/3 AKI in the first 3 days as compared to those without AKI (Mean 23700 pg/ml (SD +/- 26400) vs Mean 10700 pg/ml (SD +/- 14100). Plasma levels of ANG2 at 24h were also higher in patients who developed and persisted in Stage 3 AKI at day 3, as compared to patients who did not persist in Stage 3 AKI (Mean 41000 pg/ml (SD +/- 44800) vs Mean 15900 pg/ml (SD +/- 21700). Patients with higher plasma ANG2 levels at enrollment as well as at 24h had a higher risk for developing stage 2-3 AKI in the first 3 days. Patients with higher plasma ANG2 levels at enrollment also had a higher risk of death in the first 30 days.

Conclusions: Initial levels of ANG2 in septic shock patients have a robust association with the development of moderate-severe AKI and 30-day mortality. These findings support endothelial dysfunction as a causal pathway of AKI during sepsis.