Peri-Operative Kinetics of Plasma Mitochondrial DNA Levels during Living Donor Kidney Transplantation.
Marie KroneislNora A SpraakmanJeroen V KoomenZeinab HijaziFemke H Hoogstra-BerendsHenri G D LeuveninkMichel M R F StruysRobert H HenningGertrude J Nieuwenhuijs-MoekePublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- mitochondrial dna
- copy number
- kidney transplantation
- genome wide
- dna methylation
- anti inflammatory
- small cell lung cancer
- genome wide identification
- type diabetes
- cell death
- cell therapy
- coronary artery disease
- adipose tissue
- tyrosine kinase
- liver failure
- study protocol
- gene expression
- metabolic syndrome
- acute coronary syndrome
- bone marrow
- genome wide analysis
- molecular dynamics
- reactive oxygen species
- brain injury
- percutaneous coronary intervention
- acute ischemic stroke
- subarachnoid hemorrhage