Serum Angiopoietin-2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis

Andrew S. Allegretti, Xavier Vela Parada, Guillermo A. Ortiz, Joshua Long, Scott Krinsky, Sophia Zhao, Bryan C. Fuchs, Mozhdeh Sojoodi, Dongsheng Zhang, S. Ananth Karumanchi, Sahir Kalim, Sagar U. Nigwekar, Ravi I. Thadhani, Samir M. Parikh, Raymond T. Chung

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Acute kidney injury in decompensated cirrhosis has limited therapeutic options, and novel mechanistic targets are urgently needed. Angiopoietin-2 is a context-specific antagonist of Tie2, a receptor that signals vascular quiescence. Considering the prominence of vascular destabilization in decompensated cirrhosis, we evaluated Angiopoietin-2 to predict clinical outcomes. Serum Angiopoietin-2 was measured serially in a prospective cohort of hospitalized patients with decompensated cirrhosis and acute kidney injury. Clinical characteristics and outcomes were examined over a 90-day period and analyzed according to Angiopoietin-2 levels. Primary outcome was 90-day mortality. Our study included 191 inpatients (median Angiopoietin-2 level 18.2 [interquartile range 11.8, 26.5] ng/mL). Median Model for End-Stage Liver Disease (MELD) score was 23 [17, 30] and 90-day mortality was 41%. Increased Angiopoietin-2 levels were associated with increased mortality (died 21.9 [13.9, 30.3] ng/mL vs. alive 15.2 [9.8, 23.0] ng/mL; P < 0.001), higher Acute Kidney Injury Network stage (stage I 13.4 [9.8, 20.1] ng/mL vs. stage II 20.0 [14.1, 26.2] ng/mL vs. stage III 21.9 [13.0, 29.5] ng/mL; P = 0.002), and need for renal replacement therapy (16.5 [11.3, 23.6] ng/mL vs. 25.1 [13.3, 30.3] ng/mL; P = 0.005). The association between Angiopoietin-2 and mortality was significant in unadjusted and adjusted Cox regression models (P ≤ 0.001 for all models), and improved discrimination for mortality when added to MELD score (integrated discrimination increment 0.067; P = 0.001). Conclusion: Angiopoietin-2 was associated with mortality and other clinically relevant outcomes in a cohort of patients with decompensated cirrhosis with acute kidney injury. Further experimental study of Angiopoietin/Tie2 signaling is warranted to explore its potential mechanistic and therapeutic role in this population.

Original languageEnglish (US)
Pages (from-to)729-741
Number of pages13
JournalHepatology
Volume69
Issue number2
DOIs
StatePublished - Feb 2019
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

Fingerprint

Dive into the research topics of 'Serum Angiopoietin-2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis'. Together they form a unique fingerprint.

Cite this