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Diabetic nephropathy (DN) is a major cause of chronic kidney disease and is often diagnosed only after albuminuria or reduced kidney function becomes apparent. A study published in the Journal of Diabetes Research evaluated whether urinary extracellular vesicles (EVs) could provide biomarker signals reflecting kidney pathology in type 2 diabetes mellitus (T2DM).

The analysis examined kidney biopsy samples and urine-derived EVs from patients with T2DM and DN and from control participants without diabetes. Kidney tissue slides from five patients with T2DM and DN were compared with five control kidney tissue samples obtained from areas adjacent to suspected tumor sites. Urine samples were collected from 21 patients with T2DM and DN and 21 controls without diabetes. EVs were isolated and characterized, and NEDD4L protein expression was measured in both kidney tissue and urinary EV samples.

Urine samples from patients with DN contained a heterogeneous EV population with increased EV numbers and higher protein concentrations compared with controls. Within urinary EVs, NEDD4L protein expression was significantly reduced in patients with DN. Kidney biopsy analysis also showed reduced NEDD4L expression in tissue from patients with T2DM and DN, consistent with findings observed in urinary EV samples.

These results indicate that lower NEDD4L levels in urinary EVs reflect reduced NEDD4L expression in kidney tissue. The findings support the potential use of urinary EVs as biomarkers of T2DM-related DN.

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Key highlights

  • Urinary EV numbers and protein concentrations were higher in patients with T2DM and DN than in controls without diabetes.
  • NEDD4L protein expression in urinary EVs was significantly reduced in DN.
  • Reduced NEDD4L expression was also observed in kidney biopsy tissue from patients with DN.
  • Urinary EV NEDD4L levels reflected kidney tissue findings, supporting their potential as DN biomarkers.
Source

Thyagarajan N, Le Leu R, Kumar S, Jesudason S, Manning JA. Increased urinary extracellular vesicles and reduced expression of NEDD4L in patients with type 2 diabetes and diabetic nephropathy. J Diabetes Res. Published online March 9, 2026. doi:10.1155/jdr/3850490

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Urinary EV NEDD4L Levels Reflect Tubular Injury in Diabetic Nephropathy
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Biopsy and urine EV analysis shows reduced NEDD4L expression in patients with type 2 diabetes and diabetic nephropathy.

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