TY - JOUR
T1 - Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events After Acute Kidney Injury
AU - Mansour, Sherry G.
AU - Bhatraju, Pavan K.
AU - Coca, Steven G.
AU - Obeid, Wassim
AU - Wilson, Francis P.
AU - Stanaway, Ian Byrell
AU - Jia, Yaqi
AU - Thiessen-Philbrook, Heather
AU - Go, Alan S.
AU - Ikizler, T. Alp
AU - Siew, Edward D.
AU - Chinchilli, Vernon M.
AU - Hsu, Chi Yuan
AU - Garg, Amit X.
AU - Reeves, W. Brian
AU - Liu, Kathleen D.
AU - Kimmel, Paul L.
AU - Kaufman, James S.
AU - Wurfel, Mark M.
AU - Himmelfarb, Jonathan
AU - Parikh, Samir M.
AU - Parikh, Chirag R.
N1 - Funding Information:
This work was supported by the American Heart Association, (18CDA34110151) and Yale O’Brien Center Pilot
Funding Information:
Grant, (5P30DK079310). The ASSESS-AKI was supported by cooperative agreements from the NIDDK
Funding Information:
Care, Nestle; La Renon; Patents and Inventions: VUMC; and Scientific Advisor or Membership: Fresenius-Kabi, Kidney International. E. Siew reports Consultancy Agreements: Akebia Therapeutics on 4/19; Honoraria: Honorarium for an invited educational talk on AKI epidemiology at the DaVita Annual Physician Leadership Conference 2/19; Scientific Advisor or Membership: Editorial board of CJASN; and Other Interests/Relationships: Author for UptoDate (royalties). V. Chinchilli reports Scientific Advisor or Membership: Astra-Zeneca, Sanofi, Regeneron, Jannsen, Allergan, and Biohaven. C. Hsu reports Consultancy Agreements: as a consultant for legal cases involving acute or chronic kidney disease, consults on an ad hoc basis for companies regarding kidney disease; Research Funding: Satellite Healthcare; and Honoraria: Royalties from UpToDate, honoraria from Satellite Healthcare. A. Garg reports Research Funding: Astellas, Baxter; Scientific Advisor or Membership: Currently on the Editorial Boards of Kidney Int and AJKD; and Other Interests/Relationships: Serve on the Data Safety and Monitoring Board for an Anemia Trial Program Funded by Glaxo Smith Kline, Medical Lead Role to Improve Access to Kidney Transplantation and Living Kidney Donation for the Ontario Renal Network (government funded agency located within Ontario Health). W. Reeves reports Ownership Interest: Amgen. K. Liu reports Consultancy Agreements: AM Pharma, Biomerieux, BOA Medical, Durect, Seastar Medical; Ownership Interest: Amgen (hold stock only); and Scientific Advisor or Membership: AJRCCM, AJKD and CJASN Editorial Board; NKF Scientific Advisory Board. P. Kimmel reports Other Interests/Relationships: Co-Editor, Chronic Renal Disease Academic Press, Co-Editor, Psychosocial Aspects of Chronic Kidney Disease. Academic Press, and Royalties. J. Kaufman reports Consultancy Agreements: National Institutes of Health, National Kidney Foundation; Ownership Interest: Amgen; and Scientific Advisor or Membership: Associate Editor, American Journal of Kidney Disease; Steering Committee Chair, ASSESS-AKI, NIDDK. M. Wurfel reports Consultancy Agreements: Roche Diagnostics; Research Funding: Roche; and Honoraria: Roche Diagnostics. J. Himmelfarb reports Consultancy: Maze Therapeutics, RenalytixAI, Chinook Therapeutics, Seattle Genetics, Akebia Therapeutics, Pfizer; Honoraria: various academic institutions for invited lectures; Advisory or Leadership Role: CJASN (Ed board), BMC Medicine (Ed. Board), Nature Reviews Nephrology (Scientific Advisory Board); and Other Interests or Relationships: Research grant support from Northwest Kidney Centers, Founder and equity holder of Kuleana Technology, Inc.
Publisher Copyright:
© 2022 by ASN.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - Acute kidney injury
KW - Angiopoietin-1
KW - Angiopoietin-2
KW - Chronic kidney disease
KW - Heart failure
KW - Mortality
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U2 - 10.1681/ASN.2021060757
DO - 10.1681/ASN.2021060757
M3 - Article
C2 - 35017169
AN - SCOPUS:85125554717
SN - 1046-6673
VL - 33
SP - 613
EP - 627
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 3
ER -