Urinary extracellular vesicle RNAs as novel biomarkers for diagnosis and prognosis of lupus nephritis

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Background: Lupus nephritis (LN) is among the most serious organ manifestations of systemic lupus erythematosus (SLE), contributing significantly to morbidity and long-term renal outcomes. The development of noninvasive biomarkers capable of distinguishing active LN from non-renal SLE is of considerable clinical importance. Although renal biopsy remains the diagnostic gold standard, its invasive nature limits its utility for serial monitoring. In recent years, urine has emerged as a promising noninvasive medium for detecting renal inflammation and assessing disease activity. Methods: This study investigated whether RNA signatures within urinary extracellular vesicles (EVs) could serve as diagnostic biomarkers for LN. Urinary EVs were isolated from 27 patients with active LN and 13 with LN in remission. RNA sequencing was conducted, and four candidate transcripts were prioritized using three independent machine learning algorithms. These candidates were subsequently validated in an independent cohort comprising 143 urine samples using TaqMan-based quantitative PCR with reverse transcription (RT-qPCR). Results: Among the identified candidates, LINC01127, RUNDC3A-AS1, and LRRN3 emerged as potential diagnostic biomarkers for LN. Notably, RUNDC3A-AS1 and LRRN3 demonstrated robust discriminatory capacity between proliferative (class III/IV) and non-proliferative (class V) forms of LN. Conclusions: Our findings identify urinary extracellular vesicle RNAs-particularly LINC01127, RUNDC3A-AS1, and LRRN3-as novel, noninvasive biomarkers with potential clinical utility for the diagnosis and subclassification of LN.

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