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

Roest, Henk P., PhD1; Ooms, Liselotte S.S., MD, PhD1; Gillis, Ad J.M., BSc2; IJzermans, Jan N.M., MD, PhD1; Looijenga, Leendert H.J., PhD2; Dorssers, Lambert C.J., PhD2; Dor, Frank J.M.F., MD, PhD1,3; van der Laan, Luc J.W., PhD1

doi: 10.1097/TP.0000000000002527
Original Basic Science—General
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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.

Delayed graft function (DGF) is a complication affecting transplant outcome. In this paper the authors show that high levels of donor cell-free microRNA in the preservation fluid is associated with an increased risk of DGF after kidney transplantation.

1 Department of Surgery, Erasmus MC-University Medical Center Rotterdam, The Netherlands.

2 Department of Pathology, Laboratory For Experimental Patho-Oncology, Erasmus MC-University Medical Center Rotterdam, The Netherlands.

3 Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College, London, United Kingdom.

Received 22 June 2018. Revision received 31 October 2018.

Accepted 2 November 2018.

H.P.R., L.S.S.O., J.M.F.D., and L.J.W.vdL. contributed equally.

The authors declare no conflicts of interest.

Part of this work was supported by a grant from the Coolsingel Foundation (Stichting Coolsingel), Rotterdam, The Netherlands.

H.P.R. and L.S.S.O. performed the experiments, analyzed the data and wrote the article. A.J.M.G. participated in performing the experiments and contributed reagents. L.C.J.D. helped in analyzing the array data. L.J.H.L. provided analytical tools and helped in designing the experiments. J.W.N.I.J. participated in finalizing the draft of the manuscript. F.J.M.F.D. coinitiated the project and edited the manuscript. L.J.W.vd.L. coinitiated the project, supervised the research and edited the article.

Correspondence: Henk. P. Roest, PhD, Laboratory for Experimental Transplantation and Intestinal Surgery, Department of Surgery, Erasmus MC-University Medical Center, Room Nc-1019, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. (h.roest@erasmusmc.nl).

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