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Detection of Danger-Associated Molecular Patterns in Kidney Preservation Fluid as Predictors of Delayed Graft Function after Transplantation

Hoyos-Domingo, A.; Ruiz-Lopez, F.; Garcia-Bueno, B.; de la Torre-Alamo, M. M.; Mateo, S. V.; Vidal-Correoso, D.; Guzman Martinez-Valls, P. L.; Lopez-Abad, A.; Garcia-Rivas, F.; Lopez-Cubillana, P.; Baroja-Mazo, A.

2025-02-26 transplantation
10.1101/2025.02.25.25322862
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BackgroundKidney transplantation is the preferred treatment for end-stage renal disease, but delayed graft function remains a significant complication. Cold ischemia during organ preservation can lead to the release of danger-associated molecular patterns (DAMPs), which may influence graft outcomes. This study aimed to quantify DAMPs in kidney preservation fluid and assess their correlation with delayed graft function (DGF). MethodsPreservation fluid samples from 88 deceased kidney donors were analyzed for various DAMPs, including mitochondrial DNA (mitDNA), cytochrome c, nucleosomes, hyaluronan, and inflammasome-related molecules (IL-18 and IL-1{beta}). The influence of donor type (DBD vs. DCD) and cold ischemia time (CIT) on DAMP concentrations was evaluated. Additionally, the correlation between DAMP levels and DGF was assessed. ResultsMultiple DAMPs were detected in preservation fluid, including mitDNA, cytochrome c, nucleosomes, and hyaluronan. The type of donation (DBD vs. DCD) had minimal impact on DAMP concentrations, except for HSP70, which was significantly higher in DCD donors. CIT positively correlated with hyaluronan and nucleosome levels. Cytochrome c emerged as a potential biomarker for DGF, showing a significant increase in patients with early dysfunction and correlating with post-transplant creatinine levels. ConclusionsQuantifying DAMPs in kidney preservation fluid is feasible and may provide valuable insights into graft quality and early post-transplant outcomes. Cytochrome c, in particular, shows promise as a biomarker for predicting delayed graft dysfunction. These findings highlight the importance of minimizing cold ischemia time and suggest that DAMP analysis could improve graft assessment prior to transplantation.

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