Systemic Mitochondrial DNA Kinetics After cDCD Lung Transplantation Do Not Reflect Donor Warm Ischemic Injury: DACMEDAMPs, a Prospective multicenter translational study.

Authors

Irene Bello, Ramon Martí, Aroa Gómez-Brey, Silvana Crowley Carrasco, Maria Jesús Melià, Elena García-Arumí, Javier Pérez Vélez, Maria Deu, Sara Naranjo, Eva Fieira, Marina Pérez-Redondo, Victor Mora, Maria Ángeles Ballesteros, Fernando Mosteiro, Elisabeth Coll, Beatriz Dominguez-Gil, Alberto Sandiumenge

Published in

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. Aug 13, 2026. Epub Aug 13, 2026.

Abstract

Controlled donation after circulatory determination of death (cDCD) has markedly expanded the lung donor pool; however, the biological consequences of donor warm ischemia on mitochondrial injury and systemic danger signalling remain uncertain. Cell-free mitochondrial DNA (cf-mtDNA) has been implicated in ischemia-reperfusion injury, yet its systemic behavior in ventilated human lungs is incompletely characterized.We conducted a prospective, multicenter observational study in matched adult lung transplant recipients from cDCD and donors after brain death (DBD) to characterize donor and recipient plasma cf-mtDNA kinetics and evaluate their relationship with warm ischemic exposure.Serial plasma samples were obtained from donors and from recipients.Donor plasma cf-mtDNA levels were comparable between groups.A divergence emerged at 72 hours after transplantation, reflected by a significant donor type-by-time interaction in adjusted longitudinal analysis. Neither total nor functional warm ischemia time was associated with cf-mtDNA concentrations. In multivariable analysis restricted to 72 hours, donor type was not independently associated with absolute systemic cf-mtDNA levels. Exploratory analysis of donor-derived cf-mtDNA demonstrated a decline in graft-derived mitochondrial DNA between reperfusion and 72 hours despite a concurrent increase in total cf-mtDNA. These findings suggest that post-transplant systemic cf-mtDNA dynamics reflect recipient-driven inflammatory processes rather than a direct surrogate of donor warm ischemic injury.

PMID:
42595124
Bibliographic data and abstract were imported from PubMed on 14 Aug 2026.

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