How urine metabolomics can help in the follow-up of kidney transplant recipients: An untargeted metabolomics-based multiplatform study

Abstract Kidney transplantation (KTx) offers the best outcomes for patients with end-stage renal disease. Monitoring kidney graft function is crucial for transplant recipients (KTR) but current biomarkers are insufficient to predict kidney function evolution. This study aimed to identify new predictive biomarkers using untargeted Nuclear Magnetic Resonance (NMR) and mass spectrometry (MS)-based metabolomic approaches. In a cohort of 56 French KTR patients, urinary samples were collected 3 months post-KTx, and glomerular filtration rate (GFR) was measured at 3 and 12 months. Patients were categorized as “progressors” or “stable” based on a 7% decline or stability in kidney function over this period. Untargeted NMR- and MS-based metabolomic analyses were performed, followed by dual integration. Multivariate statistical analysis of urinary samples identified biomarker panels linked to GFR evolution. The combined approach enhanced discrimination and predictive performance (Combined platforms: Q2= 0.829, AUC= 0.845, Accuracy= 0.79 vs. NMR: Q2= 0.775, AUC= 0.794, Accuracy= 0.64). Early post-transplantation urinary metabolome analysis shows promise in predicting GFR evolution at 1 year, potentially leading to innovative tools for improving post-transplant patient care.