Identification of a serum and urine extracellular vesicle signature predicting renal outcome after kidney transplant

A long-standing effort is dedicated toward identification of biomarkers allowing the prediction of graft outcome after kidney transplant. Extracellular vesicles (EVs) circulating in body fluids represent an attractive candidate, as their cargo mirrors the originating cell and its pathophysiological status. The aim of the study was to investigate EV surface antigens as potential predictors of renal outcome after kidney transplant.

Researchers at Ente Ospedaliero Cantonale, Switzerland characterized 37 surface-antigens by flow-cytometry, in serum- and urine- EVs from 58 patients which were evaluated before, and at 10-14 days, 3 months, and 1 year after transplant, for a total of 426 analyzed samples. The outcome was defined according to estimated glomerular filtration rate (eGFR) at 1 year. Endothelial cells and platelets markers (CD31, CD41b, CD42a and CD62P) in serum-EVs were higher at baseline in patients with persistent kidney dysfunction at 1 year, and progressively decreased after kidney transplant. Conversely, mesenchymal progenitor cell marker (CD1c, CD105, CD133, SSEEA-4) in urine-EVs progressively increased after transplant in patients displaying renal recovery at follow-up. These markers correlated with eGFR, creatinine and proteinuria, associated to patient outcome at univariate analysis and were able to predict patient outcome at ROC curves analysis. A specific EV molecular signature obtained by supervised learning correctly classified patients according to 1-year renal outcome.

An EV-based signature, reflecting the cardiovascular profile of the recipient, and the repairing/regenerative features of the graft, could be introduced as a non-invasive tool for a tailored management of follow-up of patients undergoing kidney transplant.