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The emerging role of extracellular vesicles (EVs) in cell-to-cell communication and their predominant effect in the paracrine mechanisms of stem cell-dependent actions have prompted several studies on their ability to attenuate both AKI and fibrosis occurring in CKD. We discuss several critical issues that need to be addressed before EVs may have a therapeutic application in humans.For decades, stem cells and their byproducts have shown efficacy in repairing tissues and organs in numerous pre-clinical studies and some clinical trials,