*Purpose: AKI and DCD renal allografts are at high risk for DGF, yet the majority of these kidneys will eventually recover and attain good function over time. Given that DGF occurs in a tightly controlled scenario where the sequence of events and the evolution of the underlying biological phenomena can be closely monitored, the study of gene expression changes in AKI or DCD recipients provides a relevant model to investigate how the kidney repairs and regenerates after injury. This project was designed to track and identify molecular changes that occur in the peripheral blood during the initial 30 days following renal transplantation in DCD, AKI and living donor (LD) recipients. We hypothesized that: 1) the gene expression profiling in the peripheral blood of patients who have undergone renal transplantation is representative of processes undergoing in situ (within the graft), and thus: 2) will provide mechanistic insights on adaptive repair mechanisms.

*Methods: DCD (5) and AKI (4) patients were enrolled in this study. 4 LD recipients served as control. RNA-Seq analysis was performed on peripheral blood collected from these patients before the transplant and throughout the first 30 postoperative days. Bulk RNA seq was performed and, following normalization, gene expression, stratified by sample and/or time, were compared among the different groups using Partek Flow. Ingenuity pathway analysis as well as GO enrichment were performed.

*Results: Transcriptomics analysis was successfully performed on PBMC samples from AKI, DCD and LD cohorts obtained at different time points after transplantation. We stratified all samples by week and looked at differences between those patients who experienced DGF (3 among the DCD, and 2 among the AKI patients) and non-DGF outcomes. Ingenuity Pathway analysis of differentially expressed genes in all DGF samples (AKI and DCD) against non-DGF samples (AKI, DCD and LD) for weeks 1 to 4 confirmed activation of several pathway including T cell activation, dendritic and NK cell cross-talk and NFAT signaling, known to play a critical role in immune response and rejection. Eukaryotic Initiation Factor 2 (eIF2) pathway activation was significantly over-represented across all time points in the DGF group. Similarly, activation of endoplasmic reticulum (ER) stress related genes in DGF samples was over-represented at week 2 and 4 in AKI when compared to DCD cohorts.

*Conclusions: Stress related genes known to be activated in situ after damage can be found over expressed also in the peripheral blood of DGF 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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