*Purpose: The human kidney transplant (KT) patient provides a unique and compelling in situ model system to study molecular events that underlie graft recovery following transplantation. While recipients of donation after cardiac death (DCD) and acute kidney injury (AKI) grafts are more likely to experience delayed graft function than those who receive an organ from a living donor (LD), DCD/AKI allografts typically recover and resume excellent kidney function within one month post-surgery. We hypothesized that a comparative analysis of peripheral blood gene expression would reveal specific molecular mechanisms that influence the rate and degree of graft recovery.

*Methods: Transcriptome analysis (RNA-Seq) was performed on peripheral blood collected from KT patients immediately prior to transplant (D0) and at 11 time points in the first 30 days following transplantation of LD (control group), DCD or AKI (study group) donor grafts. Following normalization, data were grouped by time period (D1, D2-9, D10-25, D26-30) and expression values for each individual were compared to D0 to identify changes in gene expression compared to baseline. Following ANOVA to identify differentially expressed transcripts between AKI/DCD and LD recipients, enrichment and comparison analyses were performed to identify annotated biological pathways altered, over time, by renal transplant.

*Results: Oxidative phosphorylation was the top-ranked pathway showing a coordinated pattern of significant down-regulation for the first three weeks post-transplant, returning to near baseline in the fourth week (z-score: D2-9 = 6.565; D10-24 = 4.841; D24-31 = 1.89). Within this pathway and compared to D0, no transcripts were differentially expressed at D1, 54 genes were down-regulated and 4 were up-regulated at D2-9, 35 were genes down-regulated at D10-24, and 7 genes down-regulated at D25-31.

*Conclusions: The impairment of oxidative metabolism and mitochondrial function following acute kidney injury, and especially following ischemia reperfusion damage, has been well established however we believe this is the first study to report the recapitulation of this phenomenon in peripheral blood from KT patients. Validation of these preliminary findings in a more comprehensive cohort may allow for the identification of actionable therapeutic targets to enhance regeneration and repair of the damaged allograft.

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