Dual-Modal Serum and Urine SERS Metabolic Fingerprint for the Diagnosis and Activity Assessment of Childhood Lupus Nephritis

Lupus nephritis (LN) represents one of the most severe manifestations of childhood systemic lupus erythematosus (cSLE), often progressing rapidly and resulting in renal impairment or even end-stage renal disease. Early diagnosis and precise assessment of disease activity are essential for guiding therapy and improving clinical outcomes. However, conventional serological and urinary biomarkers exhibit limited sensitivity and specificity, while renal biopsy, although the diagnostic gold standard, is invasive and unsuitable for longitudinal monitoring. Surface-enhanced Raman spectroscopy (SERS), a noninvasive analytical approach, offers substantial potential for detecting the molecular characteristics of LNs. In this study, a high-throughput SERS microspot array plate platform was established to perform dual-modal serum and urine SERS metabolic fingerprint analyses in healthy controls ( n = 40), systemic lupus erythematosus ( n = 40), and LN patients ( n = 60). The dual-modal fusion model demonstrated superior performance over single-modal models in both LN diagnosis and disease activity assessment, achieving notably enhanced sensitivity, specificity, and overall accuracy. Furthermore, dual-modal SERS profiling revealed key biomolecular alterations associated with immune activation, inflammatory responses, and renal injury in children, providing molecular-level insights into the pathophysiological mechanisms underlying cSLE and LN.