Urinary acetylated protein as a biomarker of lupus nephritis: a prospective cohort study

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). Kidney biopsy is the gold standard for diagnosing LN. Post-translational lysine acetylation modifications have emerged as potential biomarkers. This study explored using urinary lysine-acetylated peptides as novel biomarkers for diagnosing LN and assessing activity. Urine samples were collected from patients with LN (n = 30), SLE without nephritis (n = 30), antineutrophil cytoplasmic antibody-associated glomerulonephritis (AAV-GN; n = 11), and healthy controls (n = 25). The experiment involved two steps: screening through liquid chromatography–mass spectrometry and quantifying five lysine-acetylated peptides through multiple reaction monitoring. Receiver operating characteristic analysis was used to assess the ability of these peptides to differentiate LN from other conditions. Additionally, their diagnostic value for histopathological activity was evaluated. Among the five acetylated peptides analyzed, three (ALB-K36, ALB-K161, ALB-K402) were significantly elevated in LN compared to SLE, AAV-GN, and healthy controls. Urinary ALB-K36 exhibited the highest diagnostic accuracy for LN versus AAV-GN (AUC = 0.947). These peptides remained elevated in LN patients with low proteinuria (UPCR < 500 mg/g), suggesting a potential role in early disease detection. Combining ALB-K36 with UPCR improved the diagnostic performance of histological activity index > 2 (AUC = 0.706). Urinary lysine-acetylated peptides are promising novel biomarkers for LN diagnosis and histologic assessment, complementing traditional markers, such as UPCR, and highlighting their clinical potential; however, further validation in larger cohorts is required.