Contrast-Enhanced Ultrasound to Assess Kidney Quality During

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-mediated acute kidney injury. Contrast-enhanced ultrasound (CEUS) could allow objective assessment of microvascular perfusion during renal NMP. Blood-based NMP was performed on porcine kidneys (circulatory death model) and human kidneys declined for transplant (preclinical). CEUS was performed with a contrast bolus into the NMP circuit arterial limb. Microvascular perfusion quality was quantified and z-score normalisation allowed combination of metrics and regions into an overall "CEUS-score." In porcine kidneys, inferior microvascular perfusion of cortex and medulla correlated with increased urinary NGAL (Neutrophil gelatinase-associated lipocalin) and histological DNA-fragmentation (a hallmark of apoptosis). In human kidneys, CEUS-score at 2 h was correlated with histological DNA-fragmentation (r = -0.937; P = 0.019) and predicted urinary NGAL at 24 h of NMP (r = -0.925; P = 0.024). Total renal flow was not correlated with these outcomes. An open-source web application (stingle.shinyapps.io/Time_intensity_analysis) and R package ("tican") were developed for quantitative time-intensity curve analysis. CEUS allows objective point-of-care microvascular perfusion assessment during NMP. As 2-hour CEUS-score predicts NGAL at 24 h, CEUS warrants future clinical investigation as a potential tool to assess kidney quality in assessment and reconditioning centres.