Introduction: Kidney graft transplant obtained from Brain Dead Donors (BDD) is more frequently associated with development of delayed graft function (DGF) and higher risk of rejection, compared to living donors. The mechanism(s) of BD Donors-related susceptibility to DGF is not well understood. Furthermore, identification of specific biomarkers is also crucially needed to predict the recovery of kidney function, and thus improve efficacy of graft transplant.

Objective: Major objective of this study is to evaluate components of necroptosis signaling pathway as a potential biomarkers to predict DGF. Specific components include the levels of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) in urine and serum of BD Donors.

Methods: Serum and urine samples were collected within few minutes prior to organ procurement from Brain Dead Donors. DGF was characterized by the need for hemodialysis in the first week after transplantation. Patient demographics, clinical results and outcomes were obtained accordingly with IRB approval. Studies were conducted in Alabama Organ Center and Department of Medicine, UAB.

Results: Kidneys of 36 Brain Dead Donors were transplanted into 44 individuals, of which 14 recipients developed DGF. Serum and urine levels of necroptosis markers RIPK1 and RIPK3 were significantly elevated compared to normal individuals. [table1] Serum levels of RIPK1, RIPK3 and MLKL were similar in BDD, in spite of DGF or non-DGF outcome. Interestingly, urine levels of RIPK1 and RIPK3 were significantly lower in BDD with DGF.

Conclusion: Markers of necroptosis were significantly increased in BDD. However, similar increase in the levels of RIPK1 and RIPK3 was observed in serum in both, DGF and non-DGF outcome. Notably, these markers were diminished in urine of Brain Dead Donors-related to DGF or non-DGF results. Current findings suggest that necroptosis signaling components may not be reliable predictors of DGF, however confirmatory studies will require much larger group of BD donors.

CITATION INFORMATION: Zmijewska A., Murphy J., Chen J., Zmijewski J., Mannon R. Assessing Necroptosis in Brain Dead Kidney Donors: Implications for Predicting Recipient Outcomes Am J Transplant. 2017;17 (suppl 3).

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