Novel Insights into the Molecular Mechanisms of Ischemia/Reperfusion Injury in Kidney Transplantation
Ischemia reperfusion injury (IRI) is one of the most important mechanisms involved in delayed or reduced graft function after kidney transplantation. It is a complex pathophysiological process, followed by a pro-inflammatory response that enhances the immunogenicity of the graft and the risk of acut...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Transplantology |
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| Online Access: | https://www.mdpi.com/2673-3943/2/2/18 |
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| author | Davide Loizzo Nicola Antonio di Meo Mattia Rocco Peluso Monica Rutigliano Matteo Matera Carlos Miacola Gaetano Palella Michele Tedeschi Marco Spilotros Matteo Ferro Octavian Sabin Tătaru Mihai Dorin Vartolomei Leonardo Vincenti Pasquale Ditonno Michele Battaglia Giuseppe Lucarelli |
| author_facet | Davide Loizzo Nicola Antonio di Meo Mattia Rocco Peluso Monica Rutigliano Matteo Matera Carlos Miacola Gaetano Palella Michele Tedeschi Marco Spilotros Matteo Ferro Octavian Sabin Tătaru Mihai Dorin Vartolomei Leonardo Vincenti Pasquale Ditonno Michele Battaglia Giuseppe Lucarelli |
| author_sort | Davide Loizzo |
| collection | DOAJ |
| description | Ischemia reperfusion injury (IRI) is one of the most important mechanisms involved in delayed or reduced graft function after kidney transplantation. It is a complex pathophysiological process, followed by a pro-inflammatory response that enhances the immunogenicity of the graft and the risk of acute rejection. Many biologic processes are involved in its development, such as transcriptional reprogramming, the activation of apoptosis and cell death, endothelial dysfunction and the activation of the innate and adaptive immune response. Recent evidence has highlighted the importance of complement activation in IRI cascade, which expresses a pleiotropic action on tubular cells, on vascular cells (pericytes and endothelial cells) and on immune system cells. The effects of IRI in the long term lead to interstitial fibrosis and tubular atrophy, which contribute to chronic graft dysfunction and subsequently graft failure. Furthermore, several metabolic alterations occur upon IRI. Metabolomic analyses of IRI detected a “metabolic profile” of this process, in order to identify novel biomarkers that may potentially be useful for both early diagnosis and monitoring the therapeutic response. The aim of this review is to update the most relevant molecular mechanisms underlying IRI, and also to discuss potential therapeutic targets in future clinical practice. |
| first_indexed | 2024-03-10T10:57:11Z |
| format | Article |
| id | doaj.art-0b61e35be5784b12b4c511b5a3873f50 |
| institution | Directory Open Access Journal |
| issn | 2673-3943 |
| language | English |
| last_indexed | 2024-03-10T10:57:11Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Transplantology |
| spelling | doaj.art-0b61e35be5784b12b4c511b5a3873f502023-11-21T21:45:41ZengMDPI AGTransplantology2673-39432021-05-012219120710.3390/transplantology2020018Novel Insights into the Molecular Mechanisms of Ischemia/Reperfusion Injury in Kidney TransplantationDavide Loizzo0Nicola Antonio di Meo1Mattia Rocco Peluso2Monica Rutigliano3Matteo Matera4Carlos Miacola5Gaetano Palella6Michele Tedeschi7Marco Spilotros8Matteo Ferro9Octavian Sabin Tătaru10Mihai Dorin Vartolomei11Leonardo Vincenti12Pasquale Ditonno13Michele Battaglia14Giuseppe Lucarelli15Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDivision of Urology, European Institute of Oncology (IEO)-IRCCS, 20141 Milan, ItalyThe Institution Organizing University Doctoral Studies (I.O.S.U.D.), George Emil Palade University of Medicine, Pharmacy, Sciences and Technology from Târgu Mureș, 540142 Târgu Mureș, RomaniaDepartment of Cell and Molecular Biology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology from Târgu Mureș, 540142 Târgu Mureș, RomaniaDivision of General Surgery, Polyclinic Hospital, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, ItalyIschemia reperfusion injury (IRI) is one of the most important mechanisms involved in delayed or reduced graft function after kidney transplantation. It is a complex pathophysiological process, followed by a pro-inflammatory response that enhances the immunogenicity of the graft and the risk of acute rejection. Many biologic processes are involved in its development, such as transcriptional reprogramming, the activation of apoptosis and cell death, endothelial dysfunction and the activation of the innate and adaptive immune response. Recent evidence has highlighted the importance of complement activation in IRI cascade, which expresses a pleiotropic action on tubular cells, on vascular cells (pericytes and endothelial cells) and on immune system cells. The effects of IRI in the long term lead to interstitial fibrosis and tubular atrophy, which contribute to chronic graft dysfunction and subsequently graft failure. Furthermore, several metabolic alterations occur upon IRI. Metabolomic analyses of IRI detected a “metabolic profile” of this process, in order to identify novel biomarkers that may potentially be useful for both early diagnosis and monitoring the therapeutic response. The aim of this review is to update the most relevant molecular mechanisms underlying IRI, and also to discuss potential therapeutic targets in future clinical practice.https://www.mdpi.com/2673-3943/2/2/18kidney transplantationischemia reperfusion injurycomplement systemrenal damage |
| spellingShingle | Davide Loizzo Nicola Antonio di Meo Mattia Rocco Peluso Monica Rutigliano Matteo Matera Carlos Miacola Gaetano Palella Michele Tedeschi Marco Spilotros Matteo Ferro Octavian Sabin Tătaru Mihai Dorin Vartolomei Leonardo Vincenti Pasquale Ditonno Michele Battaglia Giuseppe Lucarelli Novel Insights into the Molecular Mechanisms of Ischemia/Reperfusion Injury in Kidney Transplantation Transplantology kidney transplantation ischemia reperfusion injury complement system renal damage |
| title | Novel Insights into the Molecular Mechanisms of Ischemia/Reperfusion Injury in Kidney Transplantation |
| title_full | Novel Insights into the Molecular Mechanisms of Ischemia/Reperfusion Injury in Kidney Transplantation |
| title_fullStr | Novel Insights into the Molecular Mechanisms of Ischemia/Reperfusion Injury in Kidney Transplantation |
| title_full_unstemmed | Novel Insights into the Molecular Mechanisms of Ischemia/Reperfusion Injury in Kidney Transplantation |
| title_short | Novel Insights into the Molecular Mechanisms of Ischemia/Reperfusion Injury in Kidney Transplantation |
| title_sort | novel insights into the molecular mechanisms of ischemia reperfusion injury in kidney transplantation |
| topic | kidney transplantation ischemia reperfusion injury complement system renal damage |
| url | https://www.mdpi.com/2673-3943/2/2/18 |
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