Alban Longchamp1, Antoine Klauser2,3, Julien Songeon2, Thomas Agius1, Antonio Nastasi4, Raphael Ruttiman4, Solange Moll5, Raphael P H Meier4,6, Leo Buhler7, Jean-Marc Corpataux1, Francois Lazeyras2,3. 1. Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. 2. Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland. 3. Center for Biomedical Imaging (CIBM), Geneva, Switzerland. 4. Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland. 5. Division of Clinical Pathology, Department of Pathology and Immunology, Geneva University Hospital and Medical School, Geneva, Switzerland. 6. Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA. 7. Faculty of Science and Medicine, Section of Medicine, University of Fribourg, Switzerland.
Abstract
BACKGROUND: The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation. METHODS: To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury. RESULTS: Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. CONCLUSIONS: ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient's survival.
BACKGROUND: The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation. METHODS: To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury. RESULTS: Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. CONCLUSIONS:ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient's survival.