Mitochondrial transplantation by intra-arterial injection for acute kidney injury
| Autor: | David Zurakowski, James D. McCully, Thomas V. Rousselle, Viktoria Weixler, Isaac E. Stillman, Takashi Kido, David Blitzer, James A. H. Inkster, Alvise Guariento, Amandeep Bajwa, Mossab Y Saeed, Arzoo Orfany, Thomas Duignan, Erin Snay, Ilias P. Doulamis, Samir M. Parikh, Alan B. Packard, Pedro J. del Nido, Borami Shin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Swine Physiology Renal cortex ischemia-reperfusion injury Urology Renal function 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Medicine Acute tubular necrosis acute kidney injury mitochondrial transplantation renal Kidney Creatinine business.industry Acute kidney injury Balloon catheter Acute Kidney Injury medicine.disease Mitochondria Transplantation 030104 developmental biology medicine.anatomical_structure Injections Intra-Arterial chemistry Reperfusion Injury Female business Research Article |
| Zdroj: | Am J Physiol Renal Physiol |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00255.2020 |
| Popis: | Acute kidney injury is a common clinical disorder and one of the major causes of morbidity and mortality in the postoperative period. In this study, the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury were investigated. Female Yorkshire pigs underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon catheters. Following 60 min of ischemia, the balloon catheters were deflated and animals received either autologous mitochondria suspended in vehicle or vehicle alone, delivered as a single bolus to the renal arteries. The injected mitochondria were rapidly taken up by the kidney and were distributed throughout the tubular epithelium of the cortex and medulla. There were no safety-related issues detected with mitochondrial transplantation. Following 24 h of reperfusion, estimated glomerular filtration rate and urine output were significantly increased while serum creatinine and blood urea nitrogen were significantly decreased in swine that received mitochondria compared with those that received vehicle. Gross anatomy, histopathological analysis, acute tubular necrosis scoring, and transmission electron microscopy showed that the renal cortex of the vehicle-treated group had extensive coagulative necrosis of primarily proximal tubules, while the mitochondrial transplanted kidney showed only patchy mild acute tubular injury. Renal cortex IL-6 expression was significantly increased in vehicle-treated kidneys compared with the kidneys that received mitochondrial transplantation. These results demonstrate that mitochondrial transplantation by intra-arterial injection provides renal protection from ischemia-reperfusion injury, significantly enhancing renal function and reducing renal damage. |
| Databáze: | OpenAIRE |
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