Purpose: In kidney transplantation, allograft rejection significantly affects graft survival. The current gold standard for rejection diagnosis, biopsy, is invasive and not suited for routine monitoring. This study explores urinary metabolomics, the comprehensive analysis of endogenous metabolites in biological samples, as a non-invasive alternative to detect changes associated with transplant progression and rejection status.
Methods: We analyzed urine samples from kidney transplant recipients at two weeks and one year post-transplant, matched with biopsy results. The study involved targeted profiling of 224 metabolites using hydrophilic interaction liquid chromatography and triple quadrupole mass spectrometry (LC-MS). Statistical analysis, including Kruskal-Wallis tests, identified metabolites varying with time post-transplant and correlating with clinical status, and biological interpretation was performed using the Olaris proprietary network tool.
Results: We examined 196 urine samples from 160 recipients, categorized into 62 borderline Tcell-mediated rejections, 19 acute rejections, and 79 without acute rejection. The metabolite profiles demonstrated significant temporal variation, likely reflecting the complex interplay of post-transplant medication adjustments and physiological recovery. This suggests the critical importance of considering time-post transplant when evaluating biomarkers. Further, taurine and ethanolamine levels were markedly reduced in rejection cases, while phenylpyruvic acid,homogentisic acid, and proline were elevated. Pathway analysis highlighted alterations in phenylalanine, tyrosine, and proline metabolic pathways, some of which are known to occur in the kidney and to be disrupted when kidney function is compromised, while others may be specific to the type of injury.
Conclusions: Metabolites were shown to vary based on where a patient is in the transplant journey (early or late) and what underlying pathophysiology was occurring (rejection or no rejection). These results highlight the potential of metabolites to provide a readout of kidney graft health throughout the continuum of transplant management.