Unlabelled: The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury.
Methods: To mimic donation after circulatory death procurement, kidneys from 45-kg pigs underwent 60 min of warm ischemia. Kidneys were then perfused ex vivo for 4 h with Belzer machine perfusion solution UW at 22 °C or at 4 °C before transplantation. Magnetic resonance spectroscopic imaging coupled with LCModel fitting was used to assess energy metabolites. Kidney perfusion was evaluated with dynamic-contrast enhanced MRI. Renal biopsies were collected at various time points for histopathologic analysis.
Results: Total adenosine triphosphate content was 4 times higher during ex vivo perfusion at 22 °C than at 4 °C perfusion. At 22 °C, adenosine triphosphate levels increased during the first hours of perfusion but declined afterward. Similarly, phosphomonoesters, containing adenosine monophosphate, were increased at 22 °C and then slowly consumed over time. Compared with 4 °C, ex vivo perfusion at 22 °C improved cortical and medullary perfusion. Finally, kidney perfusion at 22 °C reduced histological lesions after transplantation (injury score: 22 °C: 10.5 ± 3.5; 4 °C: 18 ± 2.25 over 30).
Conclusions: Ex vivo kidney perfusion at 22°C improved graft metabolism and protected from ischemia-reperfusion injuries upon transplantation. Future clinical studies will need to define the benefits of subnormothermic perfusion in improving kidney graft function and patient's survival.
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http://dx.doi.org/10.1097/TXD.0000000000001354 | DOI Listing |
Mol Cell Biochem
January 2025
Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000, Kragujevac, Serbia.
As several decades of research have shown the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with diuretics, we were interested in investigating the effects of subchronic therapy of these drugs on ischemia-reperfusion (I/R) damage to the heart, as well as their influence on oxidative status. The research was conducted on 40 spontaneously hypertensive male Wistar Kyoto rats, divided into 4 groups. Animals were treated for four weeks with 10 mg/kg/day zofenopril alone or in combination with hydrochlorothiazide, indapamide and spironolactone per os.
View Article and Find Full Text PDFMol Med
January 2025
Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Background: Chronic kidney disease (CKD) is a leading cause of death in the United States, and renal fibrosis represents a pathologic hallmark of CKD. Extracellular cold-inducible RNA-binding protein (eCIRP) is a stress response protein involved in acute inflammation, tissue injury and regulated cell death. However, the role of eCIRP in chronic inflammation and tissue injury has not been elucidated.
View Article and Find Full Text PDFJ Cardiothorac Vasc Anesth
December 2024
Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL. Electronic address:
Objective: The clinical importance of individualized blood pressure management in optimizing cerebral perfusion during cardiac surgery has been well established. However, consensus on blood pressure goals is lacking. The authors studied the associations between cerebral autoregulation metrics, hemodynamic parameters, and postoperative outcomes, and hypothesized that increased time of mean arterial pressure (MAP) below the lower limit of autoregulation (LLA) is associated with major morbidity and mortality (MMOM) incidence.
View Article and Find Full Text PDFRofo
January 2025
Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany.
Multiparametric MRI is a promising technique for noninvasive structural and functional imaging of the kidneys that is gaining increasing importance in clinical research. Still, there are no standardized recommendations for analyzing the acquired images and there is a need to further evaluate the accuracy and repeatability of currently recommended MRI parameters. The aim of the study was to evaluate the test-retest repeatability of functional renal MRI parameters using different image analysis strategies.
View Article and Find Full Text PDFSci Rep
January 2025
Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Static cold storage of donor livers at 4 °C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (HS) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. HS is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations.
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