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

Mathilde Prud'homme; Maxime Coutrot; Thibault Michel; Louis Boutin; Magali Genest; Françoise Poirier; Jean-Marie Launay; Bocar Kane; Satoshi Kinugasa; Niki Prakoura; Sophie Vandermeersch; Alain Cohen-Solal; Claude Delcayre; Jane-Lise Samuel; Ravindra Mehta; Etienne Gayat; Alexandre Mebazaa; Christos E Chadjichristos; Matthieu Legrand

doi:10.1016/j.jacbts.2019.06.005

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

JACC Basic Transl Sci. 2019 Oct 28;4(6):717-732. doi: 10.1016/j.jacbts.2019.06.005. eCollection 2019 Oct.

Authors

Mathilde Prud'homme¹, Maxime Coutrot^{1

2}, Thibault Michel¹, Louis Boutin^{1

2}, Magali Genest^{1

3}, Françoise Poirier⁴, Jean-Marie Launay¹, Bocar Kane⁵, Satoshi Kinugasa³, Niki Prakoura³, Sophie Vandermeersch³, Alain Cohen-Solal^{1

6}, Claude Delcayre¹, Jane-Lise Samuel¹, Ravindra Mehta⁷, Etienne Gayat^{1

2}, Alexandre Mebazaa^{1

2}, Christos E Chadjichristos³, Matthieu Legrand^{1

2

8}

Affiliations

¹ INSERM UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Lariboisière Hospital, and INI-CRCT-F-CRIN, Paris, France.
² AP-HP, St-Louis-Lariboisière Hospital, Department of Anesthesiology and Critical Care and Burn Unit, University Paris Diderot, Paris, France.
³ INSERM UMR-S 1155, Tenon Hospital, Paris, France.
⁴ Institut Jacques Monod, Team: Morphogenesis, Homeostasis and Pathologies, Paris, France.
⁵ UMS-28 Phénotypage du petit animal, Université Pierre et Marie Curie, Paris, France.
⁶ Cardiology Department, Lariboisière Hospital, Paris, France.
⁷ Department of Medicine, University of California-San Diego, San Diego, California.
⁸ Department of Anesthesiology and peri-operative Care, University of California San Francisco, United States.

Abstract

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.

Keywords: AKI, acute kidney injury; BM, bone marrow; BUN, blood urea nitrogen; Cr, creatinine; Gal-3, galectin-3; ICAM, intercellular adhesion molecule; ICU, intensive care unit; IL, interleukin; IR, ischemia-reperfusion; KDIGO, Kidney Disease Improving Global Outcome; KO, knock-out; MCP, modified citrus pectin; NT-proBNP, N-terminal-pro-brain natriuretic peptide; TGF, transforming growth factor; TNF, tumor necrosis factor; UUO, unilateral ureteral obstruction; WT, wild type; eGFR, estimated glomerular filtration rate; fibrosis; heart failure; inflammation; macrophages; renal failure.