Characterization of Plasma Biomarkers in Brain Dead Organ Donors

Brain dead (BD) donors have been the leading source of organs for transplant. Because of the hemodynamic instability, hormonal imbalance, and increased inflammation during BD, active management is required to optimize organ function. However, there is a need to identify biomarkers that reflect organ quality and to scientifically study interventions that may improve organ quality and yield. The goal of this study is: 1) to characterize plasma gut integrity markers, bacterial translocation signals, and inflammatory cytokines in BD donors, 2) to assess changes in these markers after a period of donor management, and 3) to evaluate the association of donor biomarker levels with delayed graft function (DGF) in kidney recipients.

BD donors (n = 57) were prospectively enrolled in two cohorts. The first cohort consists of donors that were managed at local hospitals and transferred to a centralized location for organ recovery. For these donors, plasma samples were collected at the time of organ procurement. In the second cohort, donors managed and procured at a centralized donor care unit were enrolled. In this group, plasma samples were collected at the time of arrival to the unit and just prior to organ procurement. Gut integrity markers, bacterial translocation markers, inflammatory cytokines, and adhesion molecules in the plasma were quantified by ELISA and Luminex. The biomarker levels were corrected for hemodilution by normalizing to albumin levels. Comparisons were made between older and younger donors in both cohorts using Student's or Welch's t-test. Changes in biomarkers over time were measured using repeated-measures analysis of variance. Finally, donor biomarkers were compared to the presence or absence of DGF in kidney recipients.

Bacterial translocation markers were higher in older donors at the time of organ procurement and decreased less, relative to younger donors, during donor management. Inflammatory markers were initially high but decreased in most donors. Significant differences in vascular endothelial growth factor and soluble CD14 were seen in donors where DGF occurred after kidney transplant.

Bacterial translocation markers remain higher in older donors than younger donors despite donor management, while inflammatory markers have a decreasing trend in all donors. Further research is required to understand the association between these biomarkers and recipient outcomes.