MicroRNAs as Potential Markers for Advantageous Perfusion in a Preclinical Donation after Cardiac Death Animal Model of Oxygenated Hypothermic Machine Perfusion (HOPE)

Background: Extended criteria donors and donation after cardiac death donors provide organs which tend to be more sensitive to the stress of preservation. There is a lack of evidence about the potential role of oxygen in preservation techniques, and literature comparing oxygenated and non-oxygenated techniques is very limited. The aim of the study was to compare HMP with oxygen versus HMP without oxygen in a pig model of kidney auto-transplantation (KT) reproducing conditions of DCD. We have also set up miRNAs expression in preservation solution and kidney biopsies as useful biomarkers for allograft response to perfusion conditions. Methods: A randomized non blinded prospective cohorts study was established in an orthotopic auto-transplantation model mimicking Maastricht type III DCD under hypothermic machine perfusion (Life-port® kidney transporter). Real time PCR detection was performed using SYBR Green and specific commercially available probes for each miRNA of interest in preservation solution and kidney biopsies from non-oxygenated and oxygenated grafts. Sample size calculation was done attending to Mead's resource equation sample for two treatment groups. Data were expressed as median (IQA / Range) and assessed for statistical significance by Mann–Whitney U-test. Results: Somewhat better kidney function and survival results were reached in the oxygenated group. Furthermore, a selection set of miRNAs constituted by miR-29a, miR27a, miR-101, miR-126 and miR-10a, modified its expression most significantly. These miRNAs are related to cell adhesion, intracellular trafficking and kidney fibrosis, and showed a differentially expression between oxygenated and non-oxygenated HMP preservation solution of kidney grafts. Conclusions: miRNAs differential profile in preservation solution during HMP attending to oxygenation reflects a better metabolic state in oxygenated grafts. The descripted miRNAs signature could be a potential predictive biomarker of the cellular metabolic state and kidney function.