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Abstract: FR-PO006

Angiopoietin-2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Allegretti, Andrew S., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Parada, Xavier F., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Ortiz, Guillermo, St. Elizabeth's Hospital, Boston, Massachusetts, United States
  • Long, Joshua, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Krinsky, Scott, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Zhao, Sophia, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Fuchs, Bryan C., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Zhang, Dongsheng, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Karumanchi, S. Ananth, Cedars-Sinai Medical Center, Los Angeles, Massachusetts, United States
  • Kalim, Sahir, Massachusetts General Hospital/ Harvard Medical School, Cambridge, Massachusetts, United States
  • Nigwekar, Sagar U., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Thadhani, Ravi I., Cedars-Sinai, Los Angeles, California, United States
  • Parikh, Samir M., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Chung, Raymond T., Massachusetts General Hospital, Boston, Massachusetts, United States
Background

AKI 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 in a prospective cohort of hospitalized patients with decompensated cirrhosis and AKI. Clinical outcomes were examined over a 90-day period and analyzed according to Angiopoietin-2 levels. Primary outcome was 90-day mortality.

Results

We analyzed 191 patients (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 was 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), 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 AKI. Further experimental study of Angiopoietin/Tie2 signaling is warranted to explore its potential mechanistic and therapeutic role in this population.

90-day survival by Angiopoietin-2 tertile. Low (<13.5 ng/mL), Mid (13.5-23 ng/mL), High (> 23 ng/mL)

Funding

  • NIDDK Support