Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia
Abstract Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro‐inflammatory. Most studies on nephrotoxicity of hemolysis‐derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non‐protein boun...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-12-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13667 |
| _version_ | 1827584840366555136 |
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| author | Robert Greite Sebastian Schott Li Wang Lukas Gohlke Kirill Kreimann Katja Derlin Marcel Gutberlet Martina Schmidbauer Andreas Leffler Igor Tudorache Jawad Salman Fabio Ius Ruslan Natanov Christine Fegbeutel Axel Haverich Ralf Lichtinghagen Anne M. Hüsing Sibylle vonVietinghoff Roland Schmitt Nelli Shushakova Song Rong Hermann Haller Kai M. Schmidt‐Ott Magnus Gram Vijith Vijayan Irina Scheffner Wilfried Gwinner Stephan Immenschuh |
| author_facet | Robert Greite Sebastian Schott Li Wang Lukas Gohlke Kirill Kreimann Katja Derlin Marcel Gutberlet Martina Schmidbauer Andreas Leffler Igor Tudorache Jawad Salman Fabio Ius Ruslan Natanov Christine Fegbeutel Axel Haverich Ralf Lichtinghagen Anne M. Hüsing Sibylle vonVietinghoff Roland Schmitt Nelli Shushakova Song Rong Hermann Haller Kai M. Schmidt‐Ott Magnus Gram Vijith Vijayan Irina Scheffner Wilfried Gwinner Stephan Immenschuh |
| author_sort | Robert Greite |
| collection | DOAJ |
| description | Abstract Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro‐inflammatory. Most studies on nephrotoxicity of hemolysis‐derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non‐protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo‐horseradish peroxidase‐based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx), a heme scavenger‐protein. In mice, the impact of high levels of circulating free heme on the development of AKI following transient renal ischemia and the therapeutic potential of Hx were investigated. C57BL/6 mice were subjected to bilateral renal ischemia/reperfusion injury for 15 min which did not cause AKI. However, additional administration of free heme in this model promoted overt AKI with reduced renal function, increased renal inflammation, and reduced renal perfusion on functional magnetic resonance imaging. Hx treatment attenuated AKI. Free heme administration to sham operated control mice did not cause AKI. In conclusion, free heme is a predictor of AKI in CPB surgery patients and promotes AKI in transient renal ischemia. Depletion of Hx in CPB surgery patients and attenuation of AKI by Hx in the in vivo model encourage further research on Hx therapy in patients with increased free heme levels during CPB surgery. |
| first_indexed | 2024-03-08T23:37:06Z |
| format | Article |
| id | doaj.art-b6f548e5e7c54490bf7e746ba1290a06 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-03-08T23:37:06Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-b6f548e5e7c54490bf7e746ba1290a062023-12-14T06:03:04ZengWileyClinical and Translational Science1752-80541752-80622023-12-0116122729274310.1111/cts.13667Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemiaRobert Greite0Sebastian Schott1Li Wang2Lukas Gohlke3Kirill Kreimann4Katja Derlin5Marcel Gutberlet6Martina Schmidbauer7Andreas Leffler8Igor Tudorache9Jawad Salman10Fabio Ius11Ruslan Natanov12Christine Fegbeutel13Axel Haverich14Ralf Lichtinghagen15Anne M. Hüsing16Sibylle vonVietinghoff17Roland Schmitt18Nelli Shushakova19Song Rong20Hermann Haller21Kai M. Schmidt‐Ott22Magnus Gram23Vijith Vijayan24Irina Scheffner25Wilfried Gwinner26Stephan Immenschuh27Department of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyInstitute for Diagnostic and Interventional Radiology Hannover Medical School Hannover GermanyInstitute for Diagnostic and Interventional Radiology Hannover Medical School Hannover GermanyInstitute for Diagnostic and Interventional Radiology Hannover Medical School Hannover GermanyDepartment of Anesthesiology and Intensive Care Medicine Hannover Medical School Hannover GermanyDepartment of Cardiac Surgery University Hospital Dusseldorf Dusseldorf GermanyDepartment of Cardiothoracic, Transplantation and Vascular Surgery Hannover Medical School Hannover GermanyDepartment of Cardiothoracic, Transplantation and Vascular Surgery Hannover Medical School Hannover GermanyDepartment of Cardiothoracic, Transplantation and Vascular Surgery Hannover Medical School Hannover GermanyDepartment of Cardiothoracic, Transplantation and Vascular Surgery Hannover Medical School Hannover GermanyDepartment of Cardiothoracic, Transplantation and Vascular Surgery Hannover Medical School Hannover GermanyDepartment of Clinical Chemistry Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyPediatrics, Department of Clinical Sciences Lund Skane University Hospital, Lund University Lund SwedenInstitute for Transfusion Medicine and Transplant Engineering Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyDepartment of Nephrology and Hypertension Hannover Medical School Hannover GermanyInstitute for Transfusion Medicine and Transplant Engineering Hannover Medical School Hannover GermanyAbstract Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro‐inflammatory. Most studies on nephrotoxicity of hemolysis‐derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non‐protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo‐horseradish peroxidase‐based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx), a heme scavenger‐protein. In mice, the impact of high levels of circulating free heme on the development of AKI following transient renal ischemia and the therapeutic potential of Hx were investigated. C57BL/6 mice were subjected to bilateral renal ischemia/reperfusion injury for 15 min which did not cause AKI. However, additional administration of free heme in this model promoted overt AKI with reduced renal function, increased renal inflammation, and reduced renal perfusion on functional magnetic resonance imaging. Hx treatment attenuated AKI. Free heme administration to sham operated control mice did not cause AKI. In conclusion, free heme is a predictor of AKI in CPB surgery patients and promotes AKI in transient renal ischemia. Depletion of Hx in CPB surgery patients and attenuation of AKI by Hx in the in vivo model encourage further research on Hx therapy in patients with increased free heme levels during CPB surgery.https://doi.org/10.1111/cts.13667 |
| spellingShingle | Robert Greite Sebastian Schott Li Wang Lukas Gohlke Kirill Kreimann Katja Derlin Marcel Gutberlet Martina Schmidbauer Andreas Leffler Igor Tudorache Jawad Salman Fabio Ius Ruslan Natanov Christine Fegbeutel Axel Haverich Ralf Lichtinghagen Anne M. Hüsing Sibylle vonVietinghoff Roland Schmitt Nelli Shushakova Song Rong Hermann Haller Kai M. Schmidt‐Ott Magnus Gram Vijith Vijayan Irina Scheffner Wilfried Gwinner Stephan Immenschuh Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia Clinical and Translational Science |
| title | Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia |
| title_full | Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia |
| title_fullStr | Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia |
| title_full_unstemmed | Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia |
| title_short | Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia |
| title_sort | free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia |
| url | https://doi.org/10.1111/cts.13667 |
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