Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events After Acute Kidney Injury

Sherry G. Mansour, Pavan K. Bhatraju, Steven G. Coca, Wassim Obeid, Francis P. Wilson, Ian Byrell Stanaway, Yaqi Jia, Heather Thiessen-Philbrook, Alan S. Go, T. Alp Ikizler, Edward D. Siew, Vernon M. Chinchilli, Chi Yuan Hsu, Amit X. Garg, W. Brian Reeves, Kathleen D. Liu, Paul L. Kimmel, James S. Kaufman, Mark M. Wurfel, Jonathan HimmelfarbSamir M. Parikh, Chirag R. Parikh

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Background The mechanisms underlying long-term sequelae following acute kidney injury (AKI) remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for chronic kidney disease (CKD) and heart failure. Methods To investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure, as well as the secondary outcome of all-cause mortality 3 months after discharge or later. Results Median age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [95% CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression. Conclusions A higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.

Original languageEnglish (US)
Pages (from-to)613-627
Number of pages15
JournalJournal of the American Society of Nephrology
Issue number3
StatePublished - Mar 2022

All Science Journal Classification (ASJC) codes

  • General Medicine


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