Rapid sampling microdialysis as a novel tool for parenchyma assessment during static cold storage and hypothermic machine perfusion in a translational ex vivo porcine kidney model.
BACKGROUND
Viability assessment during preservation is imperative to avoid unnecessary discard of marginal organs maximizing graft outcomes in kidney transplantation. To address this need, we have developed a novel system based on a rapid sampling microdialysis (rsMD) analyzer allowing continuous tissue monitoring and measurement of metabolic markers of cell damage. Our aim was to develop a tool that allows for accurate assessment of tissue metabolism and organ viability in the preservation period.


METHODS
Twenty-two porcine kidneys subjected to 15 min of warm ischemia underwent either 24 h of static cold storage (SCS) or 10 h of hypothermic machine perfusion (HMP). After preservation, tissue temperature was allowed to passively increase to ambient temperature as an ischemic challenge. Cortical and medullary metabolism was monitored throughout with online measurements of lactate concentrations made every 60 s.


RESULTS
On commencement of monitoring, lactate concentrations were successfully detected within 15 mins. During the initial 1.5 h, lactate concentrations were similar during SCS (65 μM) and HMP (124 μM, P > 0.05) but lower after 10 h of SCS (SCS: 68 μM versus HMP: 230 μM, P < 0.001). Warming data suggest a resilience of HMP kidneys to subsequent temperature induced ischemia compared to SCS kidneys.


CONCLUSIONS
This preliminary study provides the baseline ischemic profile for porcine kidneys while validating the technique of rsMD as a tool for organ viability assessment during preservation. The data characterize metabolic differences between SCS and HMP preserved allografts and can help elucidate why HMP is clinically superior to SCS allowing development of interventions to augment these benefits.
Department of Surgery, Imperial College London, London, United Kingdom. Electronic address: karim.hamaoui08@imperial.ac.uk.
Karim
K
Hamaoui
Department of Bioengineering, Imperial College London, London, United Kingdom.
Sally
S
Gowers
Department of Surgery, Imperial College London, London, United Kingdom.
Samir
S
Damji
Department of Bioengineering, Imperial College London, London, United Kingdom.
Michelle
M
Rogers
Department of Bioengineering, Imperial College London, London, United Kingdom.
Chi Leng
CL
Leong
Department of Surgery, Imperial College London, London, United Kingdom.
George
G
Hanna
Department of Surgery, Imperial College London, London, United Kingdom.
Ara
A
Darzi
Department of Bioengineering, Imperial College London, London, United Kingdom.
Martyn
M
Boutelle
Department of Surgery, Imperial College London, London, United Kingdom; Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
Vassilios
V
Papalois
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015925:Cryopreservation / Q000379:methods*; D005240:Feasibility Studies; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation; D019344:Lactic Acid / Q000378:metabolism*; D017551:Microdialysis / Q000379:methods*; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion / Q000379:methods*; D013552:Swine; D052096:Warm Ischemia
D015415:Biomarkers; D019344:Lactic Acid
Ischaemia; Machine perfusion; Metabolism; Micro-dialysis; Preservation; Tissue viability