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Lookup NU author(s): Dr Sam Tingle, Chloe Connelly, Emily Glover, Dr George KourounisORCiD, Beth Gibson, Dr Balaji Mahendran, Lucy BatesORCiD, Madi Cooper, Rhys Pook, Sam Lee, Marnie BrownORCiD, Rodrigo Figueiredo, Professor Kevin MarchbankORCiD, Professor Simi AliORCiD, Professor Neil SheerinORCiD, Professor Colin Wilson, Dr Emily ThompsonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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 hours was correlated with histological DNA-fragmentation (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. 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 hours, CEUS warrants future clinical investigation as a potential tool to assess kidney quality in assessment and reconditioning centres.
Author(s): Tingle SJ, Connelly C, Glover EK, Stenberg B, Mcneill A, Kourounis G, Gibson BG, Mahendran B, Bates L, Cooper M, Pook R, Lee S, Brown ML, Figueiredo R, Marchbank KJ, Ali S, Sheerin N, Wilson CH, Thompson ER
Publication type: Article
Publication status: Published
Journal: Transplant International
Year: 2025
Volume: 38
Online publication date: 02/04/2025
Acceptance date: 20/03/2025
Date deposited: 21/03/2025
ISSN (print): 0934-0874
ISSN (electronic): 1432-2277
Publisher: Frontiers Media SA
URL: https://doi.org/10.3389/ti.2025.14268
DOI: 10.3389/ti.2025.14268
ePrints DOI: 10.57711/n6s0-tp68
Data Access Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
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