Acute Kidney Injury Induces Remote Cardiac Damage and Dysfunction Through the Galectin-3 Pathway

doi:10.1016/j.jacbts.2019.06.005

JACC: Basic to Translational Science

Volume 4, Issue 6, October 2019, Pages 717-732

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https://doi.org/10.1016/j.jacbts.2019.06.005 Get rights and content

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Highlights

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In 2 different mouse models, AKI increased Gal-3 expression and induced cardiac dysfunction, cardiac and systemic inflammation, cardiac macrophage infiltration, and fibrosis.
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Cardiac consequences of AKI were dependent on the Gal-3 pathway and were prevented using Gal-3 knockout mice or modified citrus pectin as a pharmaceutical inhibitor.
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Cardiac Gal-3 expression resulted from bone marrow-derived immune cells recruitment after AKI.
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In critically ill patients, development of AKI is associated with increased plasma Gal-3 levels and increased biomarkers of cardiac injury and damage.

Summary

Acute kidney injury is associated with increased risk of heart failure and mortality. This study demonstrates that acute kidney injury induces remote cardiac dysfunction, damage, injury, and fibrosis via a galectin-3 (Gal-3) dependent pathway. Gal-3 originates from bone marrow-derived immune cells. Cardiac damage could be prevented by blocking this pathway.

Visual Abstract

Key Words

fibrosis

heart failure

inflammation

macrophages

renal failure

Abbreviations and Acronyms

AKI

acute kidney injury

bone marrow

BUN

blood urea nitrogen

creatinine

eGFR

estimated glomerular filtration rate

Gal-3

galectin-3

knock-out

ICAM

intercellular adhesion molecule

ICU

intensive care unit

interleukin

ischemia-reperfusion

KDIGO

Kidney Disease Improving Global Outcome

MCP

modified citrus pectin

NT-proBNP

N-terminal-pro-brain natriuretic peptide

TGF

transforming growth factor

TNF

tumor necrosis factor

UUO

unilateral ureteral obstruction

wild type

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: This work was supported by “Institut National de la Santé et de la Recherche Médicale (INSERM)” and by Paris Diderot University and the Société Française d’Anesthésie et de Réanimation (SFAR). Dr. Prud’homme was supported by a Ph.D. training grant from Paris Diderot University and “Groupe de Réflexion sur la Recherche Cardiovasculaire (GRRC).” Dr. Cohen-Solal has received grants and fees from Novartis, Servier, Vifor, AstraZeneca, and Merck & Co. Inc. Dr. Mehta has been a consultant, a member of the advisory board for Baxter, AM Pharma, CSL-Behring, Astute Medical Inc. Regulus, Akebia, Intercept, Mallinckrodt, and Ferring; and has received grants from Relypsa, Fresenius-Kabi; Fresenius, and Grifols. Dr. Gayat has been a consultant for Magnisense and Adrenomed; and has received research grants from Deltex Medical and Retia Medical. Dr. Legrand has received research support from Sphingotec; has received lecture fees from Baxter and Fresenius; and has received consultancy fees from Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

: The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.

^∗: Drs. Coutrot, Michel, and Boutin contributed equally to this work and are joint first authors.

^†: Drs. Chadjichristos and Legrand contributed equally to this work and are joint senior authors.