The role of flavin mononucleotide (FMN) as a potentially clinically relevant biomarker to predict the quality of kidney grafts during hypothermic (oxygenated) machine perfusion.
van de Leemkolk, F. E. M., et al.PLoS ONE [Electronic Resource] 2023; 18(6): e0287713.
Aims
This study aimed to investigate the ability of flavin mononucleotide (FMN) to predict the quality of kidney grafts during hypothermic machine perfusion (HMP) with oxygenation (HMPO2).
Interventions
Kidneys were randomised to receive either HMPO2 or HMP.
Participants
197 kidney pairs (n=394) were randomised, out of which 220 were transplanted.
Outcomes
The primary outcome was the association between end of perfusion (P3) and early transplant outcomes (immediate graft function, DGF, primary non-function (PNF) and serum creatinine (SCr)) and late post-transplant outcomes (estimated creatinine clearance, graft failure and biopsy proven rejection). The secondary outcomes were associations for the P1 and P2 timepoints (beginning and during perfusion) and the delta perfusion (ΔP) with early and late posttransplant outcomes.
Follow-up
12 months posttransplantation.
CET Conclusions
This paper reports on a biomarker study conducted alongside the Consortium for Organ Preservation in Europe (COPE) study that compared Oxygenated HMP with standard HMP prior to kidney transplantation. The clinical results have been published previously (Jochmans et al 2020). Flavin Mononucleotide (FMN) is a cofactor for the mitochondrial membrane complex-I, which dissociates from the complex following ischaemia-reperfusion injury. It was therefore speculated that release of FMN in the perfusate whilst on machine perfusion may be an indicator for ischaemic injury, with some evidence in liver transplantation that correlates with poor lactate clearance and early graft loss. Analysis was done by fluorescence spectroscopy and liquid chromatography mass spectrometry. The primary analysis was to correlate FMN levels in machine perfusate immediately prior to transplantation with early and late post-transplant outcomes. Fluorescence in the FMN region was found to significantly increase during the preservation period in kidneys preserved with both oxygenated and standard HMP. As these profiles were similar, results from both groups were combined for the further analysis to increase sensitivity. Despite this approach, FMN was not found to be a clinically relevant biomarker to predict early or late graft function. The authors conducted a validation process, which suggested that the increase in fluorescence during perfusion may not be specifically related to FMN and therefore it may not be reliable perfusate biomarker in kidney transplantation.
Trial registration
ISRCTN32967929