Urinary Extracellular Vesicles Biomarkers in CKD: Clinical Laboratory Translation.

Globally, chronic kidney disease (CKD) is an increasingly prevalent public health challenge. The current kidney function tests, which include serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria, are highly useful in clinical practice. Nevertheless, they are characterized by substantial limitations that prevent the early detection of CKD. In contrast, urinary extracellular vesicles (uEVs) may offer an effective alternative for the diagnosis and monitoring of chronic kidney disease if successfully translated. Urinary extracellular vesicles are a wide range of nanosized membrane vesicles that are excreted by cells that line the nephron and urinary tract. These uEVs contain proteins, lipids, and nucleic acids that reflect the pathophysiological state of their cells of origin. This review summarizes the biological evidence for uEV biomarkers in major CKD entities, including diabetic kidney disease, FSGS, IgA nephropathy, ADPKD, and lupus nephritis. From a clinical laboratory perspective, we critically examine pre-analytical variables, analytical factors and validation requirements aligned with ISO 15189 accreditation. We discuss regulatory pathways and the balance between laboratory-developed tests and commercial IVD platforms. Moreover, we conclude that there is an essential need for reference materials, internal quality control, and external quality assessment. Finally, we outline a practical implementation pathway for transitioning uEV assays from research use to routine diagnostics. If successfully translated, uEV-based assays could facilitate earlier detection of CKD, more precise phenotyping, and personalized therapeutic monitoring.