*Purpose: Chronic kidney rejection is currently the main cause of graft losses. Blood and urine analyses to monitor kidney transplanted patients are not specific, and the gold standard diagnostic with kidney biopsy is highly invasive. Extracellular vesicles (EV) are emerging as promising carriers of biomarkers that represent the physiological or pathological state of the cells of origin and are found in all biological fluids.

*Methods: To identify biomarkers of rejection in urine, we studied the proteome of Size Exclusion Chromatography (SEC)-isolated urinary (u)EV from a cohort of kidney transplanted patients (n=37) classified in 4 groups according to their biopsy-based diagnosis: interstitial fibrosis/tubular atrophy, acute cellular rejection, calcineurin inhibitors toxicity and normal kidney function (NKF). uEVs were analysed using shotgun mass spectrometry.

*Results: After analysis with MaxQuant, Perseus (Max Plank Institute) and SPSS software for statistics, the results of this first discovery phase showed differences in the global uEV protein profile among the different groups, as well as some differentially expressed proteins. We selected 23 of those proteins for a second validation phase using targeted proteomics in a new independent cohort of patients (n=42) from a different hospital and classified in the same diagnostic groups. Four proteins were found significantly more expressed in pathology than in NKF patients, with area under the curve of tentative ROC curves >0.75. Interestingly, another particular protein was significantly highly expressed in patients with Grade-3 chronic interstitial and tubular lesions in the biopsy.

*Conclusions: Although further studies are needed, this panel of EV-related proteins could help the clinicians to improve patients’ non-invasive monitoring, reducing the need of biopsies, to extend graft and patient survival with higher life quality.

« Back to 2019 American Transplant Congress