Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Int J Mol Sci. 2023 Sep 1;24(17):13579. doi: 10.3390/ijms241713579.
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.
在缺血再灌注损伤 (IRI) 期间，线粒体可能会释放线粒体 DNA (mtDNA)。mtDNA 可以作为进一步损伤的传播者，但在特定情况下也具有抗炎能力。因此，本研究旨在研究活体供肾移植 (LDKT) 过程中血浆 mtDNA 的围手术期动态及其作为移植物预后标志物的潜力。该研究纳入了来自挥发性麻醉剂保护肾脏移植-1 试验 (VAPOR-1) 的 56 对供体-受体。在 LDKT 期间和之后的多个时间点采集了系统静脉、系统动脉和肾静脉样本。mtDNA 基因随时间和血管隔室而变化。许多供体、受体和移植相关变量显著解释了 mtDNA 基因随时间的变化。mtDNA 基因预测了 1 个月和 24 个月的估计肾小球滤过率 (eGFR) 以及 2 年随访期间的急性排斥反应事件。总之，mtDNA 在 LDKT 过程中从肾脏或全身释放到血浆中，以响应移植。虽然循环 mtDNA 水平与移植后的预后呈正相关和负相关，但确切的机制和 mtDNA 基因之间的差异尚不清楚，需要进一步探索。
