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Open Access | 10.1172/jci.insight.158523
1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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Thomas, K.
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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Mersmann, S.
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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Tekath, T.
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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1Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Muenster, Münster, Germany
2Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
3Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
4Institute of Medical Informatics, University of Münster, Münster, Germany
5Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tuebingen, Tübingen, Germany
6Critical Care Medicine, University of Pittsburgh, Pittsburgh, United States of America
7Department of Nephrology, Internal Medicine D, University of Münster, Münster, Germany
8Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
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Published June 21, 2022 - More info
Acute kidney injury increases morbidity and mortality and previous studies have shown that remote ischemic preconditioning (RIPC) reduces the risk of acute kidney injury after cardiac surgery. RIPC increases urinary HMGB1 (high mobility group box protein-1) levels in patients which correlates with kidney protection. Here, we show that RIPC reduces renal ischemia-reperfusion injury and improves kidney function in mice. Mechanistically, RIPC increases HMGB1 levels in the plasma and urine and HMGB1 binds to Toll-like receptor 4 (TLR4) on renal tubular epithelial cells, inducing transcriptomic modulation of renal tubular epithelial cells and providing renal protection, whereas TLR4 activation on non-renal cells was shown to contribute to renal injury. This protection is mediated by activation of induction of AMPK⍺ and NF-kB, which induces the upregulation of Sema5b that triggers a transient, protective G1 cell-cycle arrest. In cardiac surgery patients at high risk for postoperative acute kidney injury, increased HMGB1 and Sema5b levels after RIPC were associated with renal protection after surgery. The results may help to develop future clinical treatment options for acute kidney injury.