Strategies to Restore Adenosine Triphosphate (ATP) Level After More than 20 Hours of Cold Ischemia Time in Human Marginal Kidney Grafts
Matteo Ravaioli, Maurizio Baldassare, Francesco Vasuri, Gianandrea Pasquinelli, Maristella Laggetta, Sabrina Valente, Vanessa De Pace, Flavia Neri, Antonio Siniscalchi, Chiara Zanfi, Valentina R. Bertuzzo, Paolo Caraceni, Davide Trerè, Pasquale Longobardi, Antonio D. Pinna
Department of General Surgery and Transplantation, University of Bologna Sant’Orsola-Malpighi Hospital, Bologna, Italy
Ann Transplant 2018; 23:34-44
The persisting organ shortage in the field of transplantation recommends the use of marginal kidneys which poorly tolerate ischemic damage. Adenosine triphosphate (ATP) depletion during cold ischemia time (CIT) is considered crucial for graft function. We tested different strategies of kidney perfusion before transplantation in the attempt to improve the technique.
MATERIAL AND METHODS: Twenty human discarded kidneys from donors after brain death and with at least 20 hours of CIT were randomized to the following experimental groups (treatment time three-hours at 4°C): a) static cold storage (CS); b) static cold hyperbaric oxygenation (Hyp); c) hypothermic perfusion (PE); d) hypothermic perfusion in hyperbaric oxygenation (PE-Hyp); and e) hypothermic oxygenated perfusion (PE-O2).
RESULTS: Histological results showed that perfusion with or without oxygen did not produce any endothelial damage. A depletion of ATP content following the preservation procedure was observed in CS, PE, and Hyp, while PE-Hyp and PE-O2 were associated with a net increase of ATP content with respect to baseline level. In addition, PE-Hyp was associated with a significant downregulation of endothelial isoform of nitric oxide synthase (eNOS) gene expression and of hypoxia inducible factor-1α (HIF-1α).
CONCLUSIONS: Hyperbaric or normobaric oxygenation with perfusion improves organ metabolic preservation compared to other methods. This approach may prevent the onset of delayed graft function, but clinical trials are needed to confirm this.
Keywords: Adenosine Triphosphate, Delayed Graft Function, Organ Preservation, Organs at Risk, Pulsatile Flow