Elevated Serum Soluble Syndecan-1 Is Associated with Lupus Nephritis Flares: A Cross-Sectional Study

Lupus nephritis (LN) is a severe immune-mediated renal disorder causing significant morbidity and mortality in patients with systemic lupus erythematosus (SLE). Traditional biomarkers (serum complement components C3 and C4 and anti-dsDNA antibodies) have limited sensitivity and specificity for detecting renal flares; thus, new markers are needed to improve relapse detection and therapeutic response monitoring. We conducted a cross-sectional study including 71 women with SLE and 20 age- and sex-matched controls. Clinical data were collected, global activity was evaluated using the SLEDAI, and renal activity was evaluated using the renal SLEDAI (rSLEDAI). Serum syndecan-1 (SDC-1) and anti-dsDNA were measured using ELISA, and 24 h proteinuria was quantified. According to the rSLEDAI, 38 patients (53.5%) had LN flare, with a mean SDC-1 level of 108.5 ± 69.3 ng/mL and anti-dsDNA level of 113.1 ± 148.8 IU/mL. SDC-1 was correlated with the rSLEDAI (r = 0.32; p = 0.006), prednisone dose (r = 0.37; p = 0.002), proteinuria (r = 0.33; p = 0.005), and anti-dsDNA (r = 0.33; p = 0.006), while anti-dsDNA was positively correlated with proteinuria (r = 0.39; p = 0.001 and SDC-1 (r = 0.33; p = 0.006) and negatively correlated with age (r = -0.33; p = 0.006). High SDC-1 (cutoff ≥ 89 ng/mL) had higher sensitivity for detecting renal flares than anti-dsDNA (66% vs. 45%). In the multivariable analysis, high SDC-1 levels had around a 3-fold higher risk of being associated with LN flares, independently of anti-dsDNA and complement component levels. These results support serum SDC-1 as a promising biomarker for identifying renal flares in SLE patients, and it should be combined with traditional biomarkers to increase its value as a clinical tool. Follow-up studies are required to determine its value for predicting long-term renal outcomes.