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

ABSTRACT

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.