Urinary Exosomes as Potential Biomarkers for Diagnosis, Disease Activity Assessment, Treatment Monitoring, and...

Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus and remains a major cause of chronic kidney damage and progression to end-stage renal disease. Although kidney biopsy is considered the diagnostic gold standard, its invasive nature, risk of complications, sampling limitations, and limited suitability for repeated monitoring highlight the need for reliable non-invasive biomarkers. Urinary exosomes have emerged as a promising source of renal molecular information because they are easily accessible and contain stable bioactive molecules, including microRNAs, transfer RNA-derived fragments, messenger RNAs, long non-coding RNAs, and proteins. This review summarizes available evidence on urinary exosomal biomarkers in lupus nephritis, with particular emphasis on their potential utility in diagnosis, assessment of disease activity, monitoring of treatment response, and prognosis. The literature search was conducted in PubMed and Embase using the keywords "lupus nephritis" and "urinary exosomes". Studies were included if they investigated urinary exosomes in lupus nephritis and evaluated their relevance to disease diagnosis, activity, therapeutic response, histopathological findings, or renal outcomes. Among the analyzed biomarkers, urinary exosomal miR-146a appears to be the most consistently reported diagnostic marker, showing increased expression in active lupus nephritis and the ability to distinguish patients with renal involvement from those without nephritis. Other molecules, including selected miRNAs, tsRNAs, long RNAs, and proteins, have also shown potential clinical relevance, although their validation remains limited. Current evidence suggests that urinary exosomes may provide a non-invasive platform for improving the clinical assessment of lupus nephritis. However, most available studies are limited by small sample sizes, single-center designs, heterogeneous methodologies, and insufficient external validation. Further large-scale prospective studies are required to standardize exosome isolation and biomarker quantification and to determine whether urinary exosomal biomarker panels can complement kidney biopsy in clinical practice.