A novel urinary metabolic signature for the non-invasive screening of lupus nephritis in systemic lupus erythematosus.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that requiring early screening. This study preliminarily explored urinary metabolomic profiles to identify potential, non-invasive candidate biomarkers for the early diagnosis of LN. Urine samples were collected from 55 participants: 20 SLE patients with LN, 20 SLE patients without LN, and 15 healthy controls. Untargeted liquid chromatography-mass spectrometry (LC-MS) was utilized to determine metabolic profiles, and support vector regression was applied for data normalization. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to select optimal features, while receiver operating characteristic (ROC) curves and the area under the curve (AUC) evaluated diagnostic performance. Direct comparison between SLE patients with and without LN identified 234 differential metabolites uniquely associated with renal involvement. In the comparison between SLE patients with and without active LN, the 7-metabolite signature achieved an AUC of 0.962, indicating its potential utility as a screening tool to identify high-risk patients requiring further diagnostic workup. In conclusion, this urine-based metabolomics study reveals distinct metabolic alterations associated with renal involvement in SLE. The identified 7-metabolite signature serves as a proof-of-concept, non-invasive adjunctive biomarker toolkit, offering preliminary insights into the metabolic pathogenesis of LN while warranting future prospective validation.