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Donor Plasma Mitochondrial DNA Is Correlated with Posttransplant Renal Allograft Function

Han, Fei MD1; Wan, Shaogui MD2,3; Sun, Qipeng MD1; Chen, Nan MD3; Li, Heng MD1; Zheng, Lingling MD4; Zhang, Nana MD, PhD5; Huang, Zhengyu MD, PhD1; Hong, Liangqing MD1; Sun, Qiquan MD, PhD1

doi: 10.1097/TP.0000000000002598
Original Clinical Science–General
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Background. The lack of accurate biomarkers makes it difficult to determine whether organs are suitable for transplantation. Mitochondrial DNA (mtDNA) correlates with tissue damage and kidney disease, making it a potential biomarker in organ evaluation.

Methods. Donors who had experienced cardiac death and successfully donated their kidneys between January 2015 and May 2017 were included this study. We detected the level of mtDNA in the plasma of the donor using quantitative real-time polymerase chain reaction and then statistically analyzed the relationship between the level of mtDNA and the delayed graft function (DGF) of the recipient.

Results. The incidence of DGF or slowed graft function (SGF) increased by 4 times (68% versus 16%, P < 0.001) when the donor mtDNA (dmtDNA) level was >0.114. When dmtDNA levels were >0.243, DGF and primary nonfunction were approximately 100% and 44%, respectively. Moreover, dmtDNA was an independent risk factor for slowed graft function and DGF. A prediction model for DGF based on dmtDNA achieved an area under the receiver operating characteristic curve for a prediction score as high as 0.930 (95% confidence interval 0.856-1.000), and the validation cohort results showed that the sensitivity and specificity of the model were 100% and 78%, respectively. dmtDNA levels were correlated with 6-month allograft function (R2=0.332, P < 0.001) and 1-year graft survival (79% versus 99%, P < 0.001).

Conclusions. We conclusively demonstrated that plasma dmtDNA was an independent risk factor for DGF, which is valuable in organ evaluation. dmtDNA is a possible first predictive marker for primary nonfunction and worth further evaluation.

1 Division of Kidney Transplantation, Department of Surgery, Organ Transplantation Research Institution, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

2 Center for Molecular Pathology, The First Affiliated Hospital, Gannan Medical University, Ganzhou, China.

3 Laboratory of Cancer Biomarkers and Liquid Biopsy, Henan University, Kaifeng, China.

4 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

5 Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Received 4 September 2018. Revision received 28 November 2018.

Accepted 29 November 2018.

The authors declare no conflicts of interest.

This study was supported by the Science and Technology Project of Guangdong Province (2015B020226005), the Science and Technology Project of Guangzhou City (201604020086), the National Natural Science Foundation of China (No. 81770753, 81470978, and U1604167), the National Natural Science Foundation of Guangdong Province (No. 2015A030311040), and the Leading Scientific, Technical and Innovation Talents of the Guangdong Special Support Program (No. 2015TX01R112).

F.H. and S.W. contributed equally to this work and should be considered as co-first authors.

Q.Q.S., F.H., and S.W. designed the study, conducted all analyses, interpreted data, prepared and reviewed the article. The laboratory assays were conducted by N.C. and N.Z. Q.S., H.L., L.Z., Z.H., and L.H. participated in the data collection and edited the article.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Qiquan Sun, MD, PhD, Division of Kidney Transplantation, Department of Surgery, Organ Transplantation Research Institution, The Third Affiliated Hospital of Sun Yat-sen University, Kaichuang Rd 2693, Huangpu District, Guangzhou 510530, China. (sunqiq@mail.sysu.edu.cn).

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