Cell-free MicroRNA miR-505-3p in Graft Preservation Fluid Is an Independent Predictor of Delayed Graft Function After Kidney Transplantation

摘要

Background. Delayed graft function (DGF), a common complication after transplantation of deceased donor kidneys, affects both short-and long-term outcomes. Currently available biomarkers during graft preservation lack sensitivity in predicting risk for DGF. The aim of this study is to identify cell-free micro ribonucleic acid (miRNA) biomarkers in graft preservation fluid predictive of DGF after kidney transplantation. Methods. Vascular bed preservation fluid was collected from 48 kidney grafts from donation after circulatory death (DCD) or donation after brain death (DBD) donors. miRNA profiles were determined by polymerase chain reaction (PCR) array (n = 8) and validated by reverse transcription and quantitative PCR (n = 40). Graft function posttransplantation was defined as immediate good function (IF) or DGF. Results. A total of 223 miRNAs fulfilled the preset parameters (Ct 40 in 3 or more samples) and were included in the analysis. Thirty-two miRNAs were significantly different between DGF and IF kidney grafts (P 0.05) but, after correction for multiple testing, only miR-505-3p remained significant. The significant association of high miR-505-3p levels with DGF was confirmed in an independent validation cohort using conventional reverse transcription and quantitative PCR detection. Multivariate analyses showed miR-505-3p as an independent predictor for DGF (odds ratio, 1.12; P = 0.028). If stratified for donor type, miR-505-3p levels remained significantly different between IF and DGF in DCD grafts (P 0.01), but not in DBD grafts. Receiver operating characteristic curve analysis showed a high sensitivity and specificity (area under the curve, 0.833). Conclusions. In DCD grafts, high levels of miR-505-3p in preservation fluid are associated with increased risk of DGF after kidney transplantation. Further study is required to confirm the utility of cell-free miR-505-3p as prognostic biomarker for DGF.