Background: Early host-allograft cell-to-cell communications have been reported to occur via extracellular vesicles (EVs)/protein-miRNA complexes that might determine early allograft outcomes like delayed graft function and recovery from the acute kidney injury. In the current study we used post-reperfusion plasma EVs miRNA to determine DGF's peripheral circulating miRNA patterns and markers of graft function recovery.

Methods: A set of 62 paired pre-implantation (PI) and post-reperfusion (PR) kidney biopsies from deceased donor recipients were used for gene- and miRNA expression. PR plasma samples were used for cell-free miRNA isolation from EVs. A QPCR-array consisting of 88 miRNA involved in functions like apoptosis, immunopathology was customized based on the identified differentially expressed target gene pathways in the paired biopsy graft samples (PI and PR, respectively). Patients were classified as with/out DGF and with/out graft function recovery at 1- and 3-months post-KT. EVs miRNAs were tested in the plasma samples and analysed using web-based tool from SAbiosciences. Cel-miR-39 served as internal control and also used for normalization. Fold change (> 2), p value (< 0.05) and Ct (< 35) cutoffs were used for determining significant miRNA between groups.

Results: A panel of miRNA was differentially expressed (DE) between with/out DGF groups associated with biological functions including wound healing and regulation of immune response (miR127-3p, miR155-5p, miR370-3p, miR423-5p, miR451a). Further, there were DE miRNAs within the DGF with/out recovery groups depending on recovery at 1- and 3-months post-KT. These miRNAs included upregulation of miR 10a-5p (reported to have a high kidney specificity score implying the origin of this cell-free miRNA from allograft). Other upregulated miRNAs include miR132-3p, miR21-5p (role in regulation of inflammatory pathways). For the same group, the quantitative measure of the average of the DE miRNAs positively correlated with eGFR at 1-month (R = 0.8537; p value = 0.0016). There was similar correlation between the average delta Ct and delta eGFR (delta eGFR = the difference in eGFR at 1 week and 1 month) with R = 0.841283 and a p value of 0.0023.

Conclusion: Plasma EVs miRNA signatures early post-KT could be highly specific and sensitive non-invasive early biomarkers of graft function recovery after AKI at 1 -3 months post- KT.

CITATION INFORMATION: Bontha V, Fernandez-Pineros A, Bagchi D, Maluf D, Rhone E, Mas V. Plasma Extracellular Vesicles MicroRNA Signatures Associate with Graft Function Recovery Post-Acute Renal Allograft Injury. Am J Transplant. 2017;17 (suppl 3).

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