Ex vivo analysis of graft viability using 31P magnetic resonance imaging spectroscopy

Abstract

Abstract Objective Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]) in order to face the chronic shortage of kidneys for transplantation. However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable non-invasive means to determine kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. However, the reliability of pMRI to predict kidney energy state, and its viability before transplantation remain also unknown. Methods To mimic DCD, pig kidneys underwent 0, 30 min or 60 min of warm ischemia, before oxygenated hypothermic machine perfusion (HMP). During the ex vivo perfusion, we assessed energy metabolites and Gadolinium elimination using pMRI. Each sample underwent histopathological scoring. 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 (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. Conclusion 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 viability and patient's survival.