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 B. 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 Himmelfarb; Samir M. Parikh; Chirag R. Parikh; for the ASSESS-AKI Consortium*

doi:10.1681/ASN.2021060757

This article has a correction. Please see:

Correction: Beneficial Effects of Myo-Inositol Oxygenase Deficiency in Cisplatin-Induced AKI - March 01, 2022

Visual Abstract

Significance Statement

Mechanisms underlying long-term effects after AKI remain unclear. Because vessel instability is an early response to endothelial injury, the authors studied markers of blood vessel homeostasis (the plasma angiopoietins angiopoietin-1 and angiopoietin-2) in a multicenter prospective cohort that included 1503 adults, half of whom had AKI. Three months after hospitalization, the highest quartile of plasma angiopoietin-1:angiopoietin-2 ratio compared with the lowest quartile associated with 72% less risk of CKD progression, 94% less risk of heart failure, and 82% less risk of death among those with AKI; those without AKI exhibited similar but less pronounced reductions in risk of heart failure and mortality. Angiopoietins may serve as a common pathway to explain the progression of kidney and heart disease after AKI and may point to potential future interventions.

Abstract

Background The mechanisms underlying long-term sequelae after AKI remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for 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 and 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 [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.

View Full Text

If you are:

an ASN member, select the "ASN Member" login button.
an individual subscriber, login with you User Name and Password.
an Institutional user, select the Institution option where you will be presented with a list of Shibboleth federations. If you do not see your federation, contact publications@asn-online.org.

Log in through your institution

Purchase access

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$34.00

In order to get access to the article, you must have an account. If you have an account, enter your user name and password into the boxes above. If you do not have an account, follow the instructions below to create one. Once you have purchased the article, you will have access to it for 24 hours.

Steps for Creating an Account:

Click the "Purchase Access" button. The page will redisplay with the following message at the top of the screen. In the message, click to create an account.

When you create the account, you will be asked to register a user name, email address and you will need to create a password that is at least eight characters in length. You do not need an ASN Member number to complete the form. As you move through the registration page, you will have to verify you are a person by completing a Captcha request. Lastly, your first and last name will be required.

Once your information is successfully saved, the system will redisplay the home page of the journal. From there, navigate back to the article to purchase. Select the article and at the bottom of the page, use the credentials you just created to login. The article will be added to your shopping cart. You can continue to navigate across JASN and CJASN adding to your cart from both journals. When you are ready to complete your purchse, select the Shopping Cart from the upper right hand corner of the page and follow the onscreen instructions.