1. Introduction
ischemia, reperfusion injury, death, IRI
RENAL, ISCHEMIA, KIDNEY
These authors contributed equally to this work.During ischemia and reperfusion injury (IRI), mitochondria may release mitochondrial DNA (mtDNA). mtDNA can serve as a propagator of further injury but in specific settings has anti-inflammatory capacities as well. Therefore, the aim of this study was to study the perioperative dynamics of plasma mtDNA during living donor kidney transplantation (LDKT) and its potential as a marker of graft outcome. Fifty-six donor–recipient couples from the Volatile Anesthetic Protection of Renal Transplants-1 (VAPOR-1) trial were included. Systemic venous, systemic arterial, and renal venous samples were taken at multiple timepoints during and after LDKT. Levels of mtDNA genes changed over time and between vascular compartments. Several donor, recipient, and transplantation-related variables significantly explained the course of mtDNA genes over time. mtDNA genes predicted 1-month and 24-month estimated glomerular filtration rate (eGFR) and acute rejection episodes in the two-year follow-up period. To conclude, mtDNA is released in plasma during the process of LDKT, either from the kidney or from the whole body in response to transplantation. While circulating mtDNA levels positively and negatively predict post-transplantation outcomes, the exact mechanisms and difference between mtDNA genes are not yet understood and need further exploration.Kidney transplantation evolves in terms of quality and donor types but is also becoming more challenging, due to the use of extended criteria donors (ECD) to overcome the persisting donor shortage [Mitochondria play a central role in IRI, as they are most likely the main source of reactive oxygen species (ROS) production and represent a major effector in the regulation of cell death [It is of general interest to study innovative non-invasive strategies to reflect current or predict future graft function, as the current strategies are based on more general markers, are only a temporary reflection, or require invasive methods to assess functioning. Our aim was to study the perioperative dynamics of mtDNA by quantifying graft release and plasma levels of mtDNA during living donor kidney transplantation (LDKT) and the potential of these mtDNA levels to serve as markers of graft outcome. Three mtDNA genes were of interest due to their place and function within the mtDNA loop, namely Displacement-loop (D-loop) as part of the non-coding region, and NADH ubiquinone oxidoreductase subunit 1 (ND1) and NADH ubiquinone oxidoreductase subunit 6 (ND6) as representatives of the coding region of the mitochondrial genome. 