Different Acute Kidney Injury Patterns after Renal Ischemia Reperfusion Injury and Extracorporeal Membrane Oxygenation in Mice
The use of extracorporeal membrane oxygenation (ECMO) is associated with acute kidney injury (AKI) in thoracic organ transplantation. However, multiple other factors contribute to AKI development after these procedures such as renal ischemia-reperfusion injury (IRI) due to hypo-perfusion of the kidn...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11000 |
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| author | Robert Greite Johanna Störmer Faikah Gueler Rasul Khalikov Axel Haverich Christian Kühn Nodir Madrahimov Ruslan Natanov |
| author_facet | Robert Greite Johanna Störmer Faikah Gueler Rasul Khalikov Axel Haverich Christian Kühn Nodir Madrahimov Ruslan Natanov |
| author_sort | Robert Greite |
| collection | DOAJ |
| description | The use of extracorporeal membrane oxygenation (ECMO) is associated with acute kidney injury (AKI) in thoracic organ transplantation. However, multiple other factors contribute to AKI development after these procedures such as renal ischemia-reperfusion injury (IRI) due to hypo-perfusion of the kidney during surgery. In this study, we aimed to explore the kidney injury patterns in mouse models of ECMO and renal IRI. Kidneys of C57BL/6 mice were examined after moderate (35 min) and severe (45 min) unilateral transient renal pedicle clamping and 2 h of veno-venous ECMO. Renal injury markers, neutrophil infiltration, tubular transport function, pro-inflammatory cytokines, and renal heme oxygenase-1 (HO-1) expression were determined by immunofluorescence and qPCR. Both procedures caused AKI, but with different injury patterns. Severe neutrophil infiltration of the kidney was evident after renal IRI, but not following ECMO. Tubular transport function was severely impaired after renal IRI, but preserved in the ECMO group. Both procedures caused upregulation of pro-inflammatory cytokines in the renal tissue, but with different time kinetics. After ECMO, but not IRI, HO-1 was strongly induced in tubular cells indicating contact with hemolysis-derived proteins. After IRI, HO-1 was expressed on infiltrating myeloid cells in the tubulo-interstitial space. In conclusion, renal IRI and ECMO both caused AKI, but kidney damage after renal IRI was more pronounced including severe neutrophil infiltration and tubular transport impairment. Enhanced HO-1 expression in tubular cells after ECMO encourages limitation of hemolysis as a therapeutic approach to reduce ECMO-associated AKI. |
| first_indexed | 2024-03-09T21:43:17Z |
| format | Article |
| id | doaj.art-a0f6990f24f7452e9212229f45e71c0f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:43:17Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a0f6990f24f7452e9212229f45e71c0f2023-11-23T20:25:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191100010.3390/ijms231911000Different Acute Kidney Injury Patterns after Renal Ischemia Reperfusion Injury and Extracorporeal Membrane Oxygenation in MiceRobert Greite0Johanna Störmer1Faikah Gueler2Rasul Khalikov3Axel Haverich4Christian Kühn5Nodir Madrahimov6Ruslan Natanov7Clinic for Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, GermanyClinic for Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, GermanyClinic for Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, GermanyClinic for Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, GermanyClinic for Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, GermanyClinic for Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, GermanyClinic for Cardiac Surgery, University Hospital Würzburg, 97080 Wurzburg, GermanyClinic for Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, GermanyThe use of extracorporeal membrane oxygenation (ECMO) is associated with acute kidney injury (AKI) in thoracic organ transplantation. However, multiple other factors contribute to AKI development after these procedures such as renal ischemia-reperfusion injury (IRI) due to hypo-perfusion of the kidney during surgery. In this study, we aimed to explore the kidney injury patterns in mouse models of ECMO and renal IRI. Kidneys of C57BL/6 mice were examined after moderate (35 min) and severe (45 min) unilateral transient renal pedicle clamping and 2 h of veno-venous ECMO. Renal injury markers, neutrophil infiltration, tubular transport function, pro-inflammatory cytokines, and renal heme oxygenase-1 (HO-1) expression were determined by immunofluorescence and qPCR. Both procedures caused AKI, but with different injury patterns. Severe neutrophil infiltration of the kidney was evident after renal IRI, but not following ECMO. Tubular transport function was severely impaired after renal IRI, but preserved in the ECMO group. Both procedures caused upregulation of pro-inflammatory cytokines in the renal tissue, but with different time kinetics. After ECMO, but not IRI, HO-1 was strongly induced in tubular cells indicating contact with hemolysis-derived proteins. After IRI, HO-1 was expressed on infiltrating myeloid cells in the tubulo-interstitial space. In conclusion, renal IRI and ECMO both caused AKI, but kidney damage after renal IRI was more pronounced including severe neutrophil infiltration and tubular transport impairment. Enhanced HO-1 expression in tubular cells after ECMO encourages limitation of hemolysis as a therapeutic approach to reduce ECMO-associated AKI.https://www.mdpi.com/1422-0067/23/19/11000acute kidney injuryextracorporeal membrane oxygenationheme oxygenase-1renal inflammation |
| spellingShingle | Robert Greite Johanna Störmer Faikah Gueler Rasul Khalikov Axel Haverich Christian Kühn Nodir Madrahimov Ruslan Natanov Different Acute Kidney Injury Patterns after Renal Ischemia Reperfusion Injury and Extracorporeal Membrane Oxygenation in Mice International Journal of Molecular Sciences acute kidney injury extracorporeal membrane oxygenation heme oxygenase-1 renal inflammation |
| title | Different Acute Kidney Injury Patterns after Renal Ischemia Reperfusion Injury and Extracorporeal Membrane Oxygenation in Mice |
| title_full | Different Acute Kidney Injury Patterns after Renal Ischemia Reperfusion Injury and Extracorporeal Membrane Oxygenation in Mice |
| title_fullStr | Different Acute Kidney Injury Patterns after Renal Ischemia Reperfusion Injury and Extracorporeal Membrane Oxygenation in Mice |
| title_full_unstemmed | Different Acute Kidney Injury Patterns after Renal Ischemia Reperfusion Injury and Extracorporeal Membrane Oxygenation in Mice |
| title_short | Different Acute Kidney Injury Patterns after Renal Ischemia Reperfusion Injury and Extracorporeal Membrane Oxygenation in Mice |
| title_sort | different acute kidney injury patterns after renal ischemia reperfusion injury and extracorporeal membrane oxygenation in mice |
| topic | acute kidney injury extracorporeal membrane oxygenation heme oxygenase-1 renal inflammation |
| url | https://www.mdpi.com/1422-0067/23/19/11000 |
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