Donor Plasma Mitochondrial DNA Is Correlated with Posttransplant Renal Allograft Function

Transplantation. 2019 Nov;103(11):2347-2358. doi: 10.1097/TP.0000000000002598.

Abstract

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 (R=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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allografts / immunology
  • Biomarkers
  • DNA, Mitochondrial / blood*
  • Delayed Graft Function / etiology*
  • Delayed Graft Function / genetics
  • Female
  • Graft Rejection / epidemiology
  • Graft Survival
  • Humans
  • Immunohistochemistry
  • Incidence
  • Kidney / immunology*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / surgery
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Plasma / metabolism*
  • Postoperative Complications
  • ROC Curve
  • Retrospective Studies
  • Risk Factors
  • Tissue Donors*
  • Transplantation, Homologous / adverse effects

Substances

  • Biomarkers
  • DNA, Mitochondrial