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Flavin Mononucleotide as a Biomarker of Organ Quality-A Pilot Study
Lu Wang1, Emily Thompson1, Lucy Bates1
1Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Background:
Flavin mononucleotide (FMN), released from damaged mitochondrial complex I during hypothermic liver perfusion, has been shown to be predictive of 90-day graft loss. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) are used for organ reconditioning and quality assessment before transplantation. This pilot study aimed to investigate the changes of FMN levels during normothermic reperfusion of kidneys, livers, and lungs and examine whether FMN could serve as a biomarker to predict posttransplant allograft quality.
Methods:
FMN concentrations, in perfusates collected during NMP of kidneys, abdominal NRP, and ex vivo lung perfusion, were measured using fluorescence spectrometry and correlated to the available perfusion parameters and clinical outcomes.
Results:
Among 7 transplanted kidneys out of the 11 kidneys that underwent NMP, FMN levels at 60 minutes of NMP were significantly higher in the allografts that developed delayed graft function and primary nonfunction (P = 0.02). Fifteen livers from 23 circulatory death donors that underwent NRP were deemed suitable for transplantation. Their FMN levels at 30 minutes of NRP were significantly lower than those not procured for transplantation (P = 0.004). In contrast, little FMN was released during the 8 lung perfusions.
Conclusions:
This proof of concept study suggested that FMN in the perfusates of kidney NMP has the potential to predict posttransplant renal function, whereas FMN at 30 minutes of NRP predicts whether a liver would be accepted for transplantation. More work is required to validate the role of FMN as a putative biomarker to facilitate safe and reliable decision-making before embarking on transplantation.
Insights
Flavin mononucleotide (FMN) levels during organ perfusion can predict transplant outcomes. Higher FMN in kidney perfusates indicates poor function, while lower FMN in liver perfusates suggests suitability for transplantation.
Area of Science:
- Biochemistry
- Transplantation immunology
- Organ preservation
Background:
- Flavin mononucleotide (FMN) released from damaged mitochondria during hypothermic liver perfusion predicts graft loss.
- Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) are utilized for organ reconditioning and quality assessment.
- Investigating FMN changes during normothermic reperfusion is crucial for assessing allograft quality.
Purpose of the Study:
- To investigate Flavin mononucleotide (FMN) level changes during normothermic reperfusion of kidneys, livers, and lungs.
- To determine if FMN can serve as a biomarker for predicting posttransplant allograft quality.
- To evaluate FMN as a predictive biomarker in organ transplantation.
Main Methods:
- FMN concentrations were measured using fluorescence spectrometry in perfusates from kidney NMP, abdominal NRP, and ex vivo lung perfusion.
- Collected perfusate samples during normothermic perfusion of various organs.
- Correlated FMN levels with perfusion parameters and clinical outcomes.
Main Results:
- Higher FMN levels at 60 minutes of kidney NMP correlated with delayed graft function and primary nonfunction (P=0.02).
- Lower FMN levels at 30 minutes of liver NRP were observed in organs procured for transplantation compared to those not procured (P=0.004).
- Minimal FMN release was detected during ex vivo lung perfusion.
Conclusions:
- FMN in kidney NMP perfusates shows potential for predicting posttransplant renal function.
- FMN levels at 30 minutes of NRP can predict liver acceptance for transplantation.
- Further validation is needed to establish FMN as a reliable biomarker for pre-transplant decision-making.
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