Delayed kidney graft function (DGF) following a kidney transplant is associated with worse graft survival and higher rejection risk. Risk factors for DGF have been primarily based on clinical feature (e.g. long cold ischemia time) but are not diagnostic with 100 percent certainty. However there are no specific biomarkers to predict kidney injury and in turn provide critical information for clinical management. Prior work from several groups has documented the systemic inflammation associated with injury and ischemia. We hypothesize that specific markers of tissue injury and inflammation, including danger associated molecular pattern proteins (DAMPs) may predict risk of DGF. To test this possibility we measured the amounts of High Mobility Group Box 1 (HMGB1) in serum and urine of brain-death donors (BDD) using Western Blot analysis (Fig. 1). Among 24 donors, we found that significant increase of HMGB1 in serum (1.6 folds; P < 0.05) was associated with higher incidence of DGF. A substantial increased in HMGB1 in urine (2.1 folds; P < 0.05) was also implicated in a prevalence of DGF. These findings were consistent with the accumulation of inflammatory chemokine Monocyte Chemoattractant Protein-1 (MCP-1) in urine (2 folds; P < 0.05) measured by ELISA. However, inflammatory mediator Tumor Necrosis Factor-alpha (TNF-α) shows negligible predictability of delayed graft function. Collectively, our results suggest that HMGB1 in plasma and urine of brain death donors can be used to evaluate risk of DGF. Ongoing studies will be needed to further determine the clinical significance of HMGB1 and other DAMPs including correlation between DGF and time of kidney acquisition from brain death donors.

CITATION INFORMATION: Zmijewska A, Chen J, Locke J, Zmijewski J, Mannon R. Release of HMGB1 in Serum and Urine of Brain-Death Donors Is Associated with Delayed Graft Function (DGF) of the Kidney. Am J Transplant. 2017;17 (suppl 3).

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