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Serum Angiopoietin-2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis.
Hepatology. 2018 Aug 23;:
Authors: Allegretti AS, Parada XV, Ortiz GA, Long J, Krinsky S, Zhao S, Fuchs BC, Sojoodi M, Zhang D, Ananth Karumanchi S, Kalim S, Nigwekar SU, Thadhani RI, Parikh SM, Chung RT
Abstract
BACKGROUND/AIMS: 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.
METHODS: 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.
RESULTS: Our study included 191 inpatients (median Angiopoietin-2 level 18.2 [IQR 11.8, 26.5] ng/mL). Median 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 AKIN 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 decompensated cirrhotic patients with acute kidney injury. Further experimental study of Angiopoietin/Tie2 signaling is warranted to explore its potential mechanistic and therapeutic role in this population. This article is protected by copyright. All rights reserved.
PMID: 30141205 [PubMed - as supplied by publisher]