Research Paper Volume 13, Issue 6 pp 8440—8453

Donor plasma mitochondrial DNA is associated with antibody-mediated rejection in renal allograft recipients

Fei Han1, *,#, , Qipeng Sun1, *,#, , Zhengyu Huang1, *,#, , Heng Li1, , Maolin Ma1, , Tao Liao1, , Zihuang Luo1, , Lingling Zheng2, , Nana Zhang3, , Nan Chen4, , Liangqing Hong1, , Ning Na1, , Qiquan Sun1, ,

  • 1 Organ Transplantation Research Institution, Division of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
  • 2 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, China
  • 3 Department of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
  • 4 Laboratory of Cancer Biomarkers and Liquid Biopsy, Henan University, Kaifeng, China
* Equal contribution
# Co-first authors

Received: November 13, 2020       Accepted: January 22, 2021       Published: March 10, 2021      

https://doi.org/10.18632/aging.202654
How to Cite

Copyright: © 2021 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We previously showed that donor plasma mitochondrial DNA (dmtDNA) levels were correlated with renal allograft function. The aim of the current study was to determine whether dmtDNA levels are associated with the occurrence of antibody-mediated rejection (ABMR). This is a retrospective open cohort study comprised of 167 donors and 323 recipients enrolled from January 2015 to December 2017. We quantified the mtDNA level present in donor plasma using quantitative real-time polymerase chain reaction. The average plasma dmtDNA level in the acute rejection (AR) group was higher than that of the control group (0.156 versus 0.075, p<0.001). Multivariate logistic regression analysis showed that dmtDNA levels were also significantly associated with AR (OR=1.588, 95% CI 1.337-4.561, p<0.001). When the dmtDNA level was >0.156, the probability of AR was 62.9%. The plasma dmtDNA level in the ABMR group was significantly higher than that of the T cell-mediated rejection group (0.185 versus 0.099, p=0.032). The area under the receiver operating characteristic curve of dmtDNA for prediction of ABMR was as high as 0.910 (95% CI 0.843-0.977). We demonstrated that plasma dmtDNA was an independent risk factor for ABMR, which is valuable in organ evaluation. dmtDNA level is a possible first predictive marker for ABMR.

Abbreviations

dmtDNA: donor mitochondrial DNA; ABMR: antibody-mediated rejection; TCMR: T cell-mediated rejection group; AKI: acute kidney injury; BMI: body mass index; IGF: immediate graft function; DGF: delayed graft function; GN: glomerulonephritis; PKD: polycystic kidney disease; HD: hemodialysis; PD: peritoneal dialysis; HLA: human leukocyte antigen; SCr: serum creatinine; CI: confidence interval; OR: odds ratio; ECD: expanded criteria donors; ESRD: end-stage renal disease; WIT: warm ischemia time; CIT: cold ischemia time.