Quantifying Flavin mononucleotide: an internationally validated methodological approach for enhanced decision making in organ transplantation.

Philipp C Müller, Tobias Diwan, Khaled Ali, Lorenzo A Cadinu, Beatrice Cazzaniga, Yuki Miyazaki, Alejandro Pita, Mazhar Khalil, JaeKeun Kim, Femke H C De Goeij, David H C Kwon, Eduardo Fernandes, Jacek Cywinski, Lidong Sun, Philipp Dutkowski, Robert L Fairchild, Jeroen De Jonge, David Meierhofer, Omer F Karakaya, Charles Miller, Andrea Schlegel, Rebecca Panconesi, Sangeeta Satish, Chunbao Jiao, Keyue Sun, Chase J Wehrle, Qiang Liu, Ahmed Hussein, Antonio Pinna, Jamak Modaresi Esfeh, Masato Fujiki, Koji Hashimoto, Federico Aucejo

Journal: EBioMedicine 2025;116():105761

PMID: 40435722

Free Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Increasing donor risk, particularly in liver transplantation, where organs are often marginal, has made dynamic organ preservation techniques and viability assessment essential to safely improve organ quality and increase utilisation. However, existing viability parameters are based on routine clinical assessment in patients with acute liver failure, trauma, or liver resections. These parameters often do not correlate with clinically relevant post-transplant outcomes.

METHODS

This article presents a detailed protocol for the spectrophotometric quantification of Flavin mononucleotide (FMN), a marker of mitochondrial injury. FMN release from mitochondrial complex I was described many decades ago as the initial sign of ischaemia-reperfusion injury, i.e. when oxygen is reintroduced in ischaemic tissues during organ transplantation or machine perfusion. This study describes the detailed FMN quantification in donor plasma and various fluids obtained during machine perfusion, and discusses confounders, challenges, and the role of individual test components.

FINDINGS

FMN quantification was identified as an immediate organ assessment tool, demonstrating a strong correlation with graft survival and other relevant complications after human liver transplantation.

INTERPRETATION

The results highlight FMN quantification as a reliable and standardized method for assessing organ viability, offering significant potential for improving organ selection and better utilisation. This method could provide better a predictive value for transplant outcomes compared to existing parameters currently in use.

FUNDING

This research received no external funding but was supported by the Catalyst grant No. CCG0280 at Cleveland Clinic Ohio, U.S. dedicated to A.S.

Address: Department of Inflammation & Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Department of Inflammation & Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Transplantation Center, Cleveland Clinic, Cleveland, OH, USA.; Department of Surgery, Division of Hepato-pancreato-biliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Transplantation Center, Cleveland Clinic, Cleveland, OH, USA.; Department of Electric and Electronic Engineering, University of Cagliari, Via Marengo 2, 09123, Cagliari, Italy.; Department of Liver Transplantation, Cleveland Clinic Weston Hospital, Weston, FL, USA.; Department of Visceral Surgery, University Hospital Basel, Switzerland.; Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, OH, USA.; Anesthesia Institute, Cleveland Clinic, Cleveland, OH, USA.; Institute of Experimental Physics, Johannes Kepler University Linz, Austria.; Max Planck Institute for Molecular Genetics, Mass Spectrometry Facility, 14195, Berlin, Germany.; Department of Inflammation & Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Transplantation Center, Cleveland Clinic, Cleveland, OH, USA. Electronic address: [email protected].

DOI: 10.1016/j.ebiom.2025.105761

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/livertransplantation.html

Subscription / membership required

Full Text Sources:

https://www.clinicalkey.com/content/playBy/pii?v=S...

MeSH Terms: Humans, Flavin Mononucleotide, Liver Transplantation, Organ Transplantation, Biomarkers, Organ Preservation, Reperfusion Injury, Graft Survival, Decision Making, Perfusion, Clinical Decision-Making