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.
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.
Authors: Hendrik Gremmels; Olivier G de Jong; Raechel J Toorop; Laura Michielsen; Arjan D van Zuilen; Alexander V Vlassov; Marianne C Verhaar; Bas W M van Balkom Journal: Transplant Direct Date: 2019-08-12
Authors: João Lobo; Ad J M Gillis; Annette van den Berg; Lambert C J Dorssers; Gafanzer Belge; Klaus-Peter Dieckmann; Henk P Roest; Luc J W van der Laan; Jourik Gietema; Robert J Hamilton; Carmen Jerónimo; Rui Henrique; Daniela Salvatori; Leendert H J Looijenga Journal: Cells Date: 2019-12-14 Impact factor: 6.600
Authors: Floris J M Roos; Monique M A Verstegen; Laura Muñoz Albarinos; Henk P Roest; Jan-Werner Poley; Geert W M Tetteroo; Jan N M IJzermans; Luc J W van der Laan Journal: Front Cell Dev Biol Date: 2021-02-09
Authors: Floris J M Roos; Haoyu Wu; Jorke Willemse; Ruby Lieshout; Laura A Muñoz Albarinos; Yik-Yang Kan; Jan-Werner Poley; Marco J Bruno; Jeroen de Jonge; Richard Bártfai; Hendrik Marks; Jan N M IJzermans; Monique M A Verstegen; Luc J W van der Laan Journal: Clin Transl Med Date: 2021-12