54 Contrast-enhanced ultrasound to assess kidney quality during ex situ normothermic machine perfusion

Abstract Background Normothermic machine perfusion (NMP) provides opportunity for viability assessment of donated kidneys. Diminished microvascular perfusion, despite adequate total blood flow, is a key pathophysiology in ischaemia reperfusion injury mediated acute kidney injury. Contrast-enhanced ultrasound (CEUS) could allow assessment of microvascular perfusion during renal NMP. Methods Blood-based NMP was performed on porcine kidneys, and human kidneys declined for transplant (REC15/SC/0161). Porcine kidneys were retrieved with a circulatory death model. CEUS was performed with Philips EPIQ7 Ultrasound machine and sulphur hexafluoride contrast agent, delivered as a bolus into the NMP circuit arterial limb. Microvascular perfusion quality was quantified with peak and time-to-peak values. Z-score normalisation allowed combination of cortex/medulla scores into an overall “CEUS-score”. Results In porcine kidneys (n=8), decreased quality of perfusion in renal cortex and medulla was correlated with urinary NGAL (Pearson r=0.900; P=0.002 and r=0.745; P=0.034, respectively) and tissue apoptosis (r=0.647; P=0.083 and r=0.805; P=0.016). These findings were confirmed in human kidneys (n=5). In human kidneys, “CEUS-score” at 2 hours was correlated with tissue apoptosis (r=-0.937; P=0.019) and predicted urinary NGAL at 24 hours of NMP (r=-0.925; P=0.024). Total renal flow was not correlated with these outcomes. A web app (stingle.shinyapps.io/Time_intensity_analysis) and R package (“tican”) were developed for quantitative CEUS analysis. Conclusion CEUS allows point-of-care assessment of microvascular perfusion during renal NMP, which correlates with tissue apoptosis on histology. 2-hour CEUS-score predicts the key biomarker urinary NGAL at 24 hours of NMP in human kidneys. Techniques for CEUS-quantification were developed and disseminated via open-source software.