The protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery

Christian Stoppe; Luisa Averdunk; Andreas Goetzenich; Josefin Soppert; Arnaud Marlier; Sandra Kraemer; Jil Vieten; Mark Coburn; Ana Kowark; Bong-Song Kim; Gernot Marx; Steffen Rex; Akinobu Ochi; Lin Leng; Gilbert Moeckel; Andreas Linkermann; Omar El Bounkari; Alexander Zarbock; Jürgen Bernhagen; Sonja Djudjaj; Richard Bucala; Peter Boor

doi:10.1126/scitranslmed.aan4886

Research ArticleKidney Disease

The protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery

Christian Stoppe ¹,*,†,
Luisa Averdunk¹,*,
Andreas Goetzenich²,
Josefin Soppert¹,²,
Arnaud Marlier³,
Sandra Kraemer²,
Jil Vieten¹,
Mark Coburn⁴,
Ana Kowark⁴,
Bong-Song Kim⁵,
Gernot Marx¹,
Steffen Rex⁶,
Akinobu Ochi⁷,
Lin Leng⁸,
Gilbert Moeckel⁷,
Andreas Linkermann⁹,
Omar El Bounkari¹⁰,
Alexander Zarbock¹¹,
Jürgen Bernhagen¹⁰,¹²,¹³,†,
Sonja Djudjaj¹⁴,‡,
Richard Bucala ⁸,‡ and
Peter Boor ¹⁴,¹⁵,†,‡

¹Department of Intensive Care Medicine, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.
²Department of Thoracic, Cardiac and Vascular Surgery, University Hospital, RWTH Aachen, Aachen, Germany.
³Department of Nephrology, Yale University School of Medicine, New Haven, CT 06510, USA.
⁴Department of Anesthesiology, University Hospital, RWTH Aachen, Aachen, Germany.
⁵Department of Plastic and Reconstructive Surgery, Hand Surgery, Burn Center, RWTH Aachen, Aachen, Germany.
⁶Department of Anesthesiology, University Hospitals Leuven, Leuven, Belgium.
⁷Department of Nephropathology, Yale University School of Medicine, New Haven, CT 06520, USA.
⁸Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
⁹Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
¹⁰Department of Vascular Biology, Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany.
¹¹Department of Anesthesiology, Critical Care Medicine and Pain Therapy, University Hospital Münster, Münster, Germany.
¹²German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
¹³Munich Cluster for Systems Neurology (EXC 1010 SyNergy), Munich, Germany.
¹⁴Institute of Pathology and Department of Nephrology, University Hospital, RWTH Aachen, Aachen, Germany.
¹⁵Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia.

↵†Corresponding author. Email: christian.stoppe{at}gmail.com (C.S.); juergen.bernhagen{at}med.uni-muenchen.de (J.B.); pboor{at}ukaachen.de (P.B.)

↵* These authors contributed equally as first authors.
↵‡ These authors contributed equally as last authors.

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Science Translational Medicine 16 May 2018:
Vol. 10, Issue 441, eaan4886
DOI: 10.1126/scitranslmed.aan4886

Christian Stoppe

Department of Intensive Care Medicine, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.

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ORCID record for Christian Stoppe
For correspondence: christian.stoppe@gmail.com juergen.bernhagen@med.uni-muenchen.de pboor@ukaachen.de

Luisa Averdunk

Department of Intensive Care Medicine, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.

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Andreas Goetzenich

Department of Thoracic, Cardiac and Vascular Surgery, University Hospital, RWTH Aachen, Aachen, Germany.

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Josefin Soppert

Department of Intensive Care Medicine, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.Department of Thoracic, Cardiac and Vascular Surgery, University Hospital, RWTH Aachen, Aachen, Germany.

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Arnaud Marlier

Department of Nephrology, Yale University School of Medicine, New Haven, CT 06510, USA.

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Sandra Kraemer

Department of Thoracic, Cardiac and Vascular Surgery, University Hospital, RWTH Aachen, Aachen, Germany.

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Jil Vieten

Department of Intensive Care Medicine, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.

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Mark Coburn

Department of Anesthesiology, University Hospital, RWTH Aachen, Aachen, Germany.

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Ana Kowark

Department of Anesthesiology, University Hospital, RWTH Aachen, Aachen, Germany.

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Bong-Song Kim

Department of Plastic and Reconstructive Surgery, Hand Surgery, Burn Center, RWTH Aachen, Aachen, Germany.

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Gernot Marx

Department of Intensive Care Medicine, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.

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Steffen Rex

Department of Anesthesiology, University Hospitals Leuven, Leuven, Belgium.

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Akinobu Ochi

Department of Nephropathology, Yale University School of Medicine, New Haven, CT 06520, USA.

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Lin Leng

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.

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Gilbert Moeckel

Department of Nephropathology, Yale University School of Medicine, New Haven, CT 06520, USA.

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Andreas Linkermann

Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.

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Omar El Bounkari

Department of Vascular Biology, Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany.

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Alexander Zarbock

Department of Anesthesiology, Critical Care Medicine and Pain Therapy, University Hospital Münster, Münster, Germany.

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Jürgen Bernhagen

Department of Vascular Biology, Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany.German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.Munich Cluster for Systems Neurology (EXC 1010 SyNergy), Munich, Germany.

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For correspondence: christian.stoppe@gmail.com juergen.bernhagen@med.uni-muenchen.de pboor@ukaachen.de

Sonja Djudjaj

Institute of Pathology and Department of Nephrology, University Hospital, RWTH Aachen, Aachen, Germany.

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Richard Bucala

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.

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Peter Boor

Institute of Pathology and Department of Nephrology, University Hospital, RWTH Aachen, Aachen, Germany.Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia.

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For correspondence: christian.stoppe@gmail.com juergen.bernhagen@med.uni-muenchen.de pboor@ukaachen.de

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MIF muffles kidney injury

Patients undergoing open-heart surgery are susceptible to complications, including acute kidney injury (AKI). Stoppe et al. observed that patients who had high serum concentrations of macrophage migration inhibitory factor (MIF) after cardiac surgery had lower risk of AKI. Renal ischemia-reperfusion injury induced more inflammation and kidney cell death in mice lacking Mif than in wild-type mice. Treating isolated kidney cells with MIF protected against hypoxia-induced cell death. Mice treated with MIF or a soluble form of CD74 (MIF receptor) showed reduced kidney injury after ischemia-reperfusion. This study suggests that MIF may protect the kidney from ischemia-reperfusion injury.

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Clinical data after cardiac surgery and experimental mouse models of acute kidney injury suggest a renoprotective role of macrophage migration inhibitory factor (MIF).

The protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery

MIF muffles kidney injury

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