Within EVs, NEDD4L protein expression was significantly reduced in patients with DN as compared with controls without diabetes.<h4>Conclusion</h4>We reported a higher concentration of a heterogeneous population of urinary EVs in patients with T2DM and DN, with decreased NEDD4L protein levels that reflect the findings observed in the kidney biopsy samples of such patients. This evidence concerns the gene NEDD4L and diabetes mellitus.