*Purpose: Presently, a definitive diagnosis of organ dysfunction after transplantation (such as acute rejection) is dependent on conventional histopathological evaluation using an invasive biopsy procedure because blood or imaging studies cannot conclusively diagnose such conditions. Recently, the usefulness of liquid biopsy has been highlighted. This technique involves a minimally invasive approach to collect samples, such as saliva, urine, or blood, which can be evaluated frequently without over-burdening the patient. Metabolomics is one of the omics technologies which enable simultaneous identification and quantifications of hundreds of metabolites. This method has been employed to find these biomarker discoveries using biofluid samples. Here, we utilized metabolomics technologies to discover new biomarkers of acute kidney rejection after transplantation.

*Methods: Kidney transplant patients followed up at our hospital were grouped into 3 groups as follows; kidney transplant donors (healthy subjects, n=9), subjects with normal kidney function after kidney transplantation (n=19), and subjects with impaired kidney function after kidney transplantation (n=32). Pathological diagnosis of this group included T cell-mediated acute rejection (AR) (n=10), antibody-mediated rejection (n=8), calcineurin inhibitor nephropathy (n=3), and the other causes of graft function (n=8). Metabolome analysis was performed on 60 blood, urine and saliva specimens from the subjects. The results of the metabolome analysis were compared with the definitive diagnoses made by using kidney graft biopsy.

*Results: In the group of subjects with impaired kidney function after kidney transplantation, 8 substances in blood (asymmetrical dimethylarginine [ADMA], diethanolamine, glycerophosphorylcholine, isocitrate, phenylalanine, symmetrical dimethylarginine [SDMA], serotonin, and valine) and 3 substances in urine (3-indoxy sulfate, ADMA, and N-acetylhistidine) and 7 substances in saliva (2-hydroxyglutarate, adipate, ethanolamine phosphate, fumalate, glycolate, proline, sedoheptulose 7-phosphate) that were significantly different (p<0.001) from those in the control group, the normal kidney function after kidney transplantation, and the group of kidney transplant donors.

*Conclusions: The Salivary test has significant advantages compared to the blood-based test, which can be performed frequently due to its non-invasiveness. Such AR diagnosis methods would be useful as a clinical application.

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