Untargeted NMR-based metabolomics analysis of kidney allograft perfusates identifies a signature of delayed graft function.

INTRODUCTION: Kidney transplantation (KTx) necessarily conveys an ischemia/reperfusion (I/R) process, which impacts on allograft outcomes. Delayed graft function (DGF) is defined as a non-decrease of serum creatinine by at least 10% daily on 3 consecutive days during the first 7 days post-KTx. DGF significantly conditions both short- and long-term graft outcomes. Still there is a lack of DGF predictive biomarkers. OBJECTIVES: This study aimed to explore the potential of kidney graft perfusate metabolomics to predict DGF occurrence. METHODS: 49 human perfusates from grafts categorized upon donor type [donation after brain death (DBD)/donation after circulatory death (DCD)] and DGF occurrence and 19 perfusates from a murine model classified upon death type (DBD/DCD) were collected and analyzed by NMR-based metabolomics. RESULTS: The multivariate analysis of the murine data highlighted significant differences between perfusate metabolomes of DBD versus DCD. These differences were similarly observed in the human perfusates. After correcting for the type of donor, multivariate analysis of human data demonstrated a metabolomics signature that could be correlated with DGF occurrence. CONCLUSIONS: The metabolome of kidney grafts is influenced by the donor's type in both human and pre-clinical studies and could be correlated with DGF in the human DBD cohort. Thus, metabolomic analysis of perfusate applied prior to KTx may represent a new predictive tool for clinicians in a more personalized management of DGF. Moreover, our data paves the way to better understand the impact of donor's types on the biochemical events occurring between death and the hypothermic storage.

[Mesenchymal stromal cells and organ transplantation]. / Cellules stromales mésenchymateuses et transplantation d'organes.

Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of isehemic injury, and for their potential properties of tissue or organ reconstruction. Over the last few years, the potential role of MSC in organ transplantation has been studied both in vitro and in vivo, and their properties make them an ideal potential cell therapy after solid organ transplantation. A prospective, controlled, phase 1-2 study has been initiated at the CHU of Liege, Belgium. This study assesses the potential risks and benefits of MSC infusion after liver or kidney transplantation. Even if the preliminary results of this study look promising, solely a prospective, randomized, large scale, phase 3 study will allow the clinical confirmation of the theoretical benefits of MSC in solid organ transplantation.