Clinical associations with serum syndecan-1 level in patients with lupus nephritis

Abstract

Background: Cardiovascular disease is an important long-term complication in patients with lupus nephritis. The endothelial glycocalyx regulates the adhesiveness of circulating cells to vascular endothelial cells and vascular permeability. Syndecan-1 is a component of the endothelial glycocalyx, and syndecan-1 shedding occurs in endothelial cell activation or injury. Methods: Serial serum samples from patients with biopsy-proven Class III/IV lupus nephritis were obtained at intervals of 3-4 months over two years. In addition, paired samples with one obtained during flare and the other during remission were included. Sera from age- and sex-matched patients with IgA nephropathy (IgAN), SLE patients without nephritis, and healthy subjects were included as controls (n=25 for each group). Serum syndecan-1 level was determined by ELISA. Results: Four hundred and sixty sera from 29 lupus nephritis patients (20 females and 9 males; age 39.0±10.2 years; disease duration 7.6±8.6 years) were studied. Serum syndecan-1 level was significantly higher during active lupus nephritis compared with remission, and also the IgAN, non-renal lupus, and healthy control groups (P<0.001, for all). Syndecan-1 level correlated with SLEDAI (r=0.535, P<0.001), anti-dsDNA antibody level (r=0.407, P=0.003), serum creatinine level (r=0.262, P=0.05), proteinuria (r=0.571, P<0.001), and inversely correlated with serum C3 (r=-0.443, P=0.001) and albumin levels (r=-0.568, P<0.001). Circulating syndecan-1 level showed a temporal relationship with disease activity and changes in anti-dsDNA antibody and C3 levels. ROC curve analysis showed that serum syndecan-1 level distinguished active lupus nephritis from healthy subjects with sensitivity and specificity rates of 96.3% and 96.0% respectively, from IgAN patients with respective rates of 85.2% and 91.3%, and from non-renal lupus patients with respective rates of 85.7% and 70.4% (P<0.0001, for all). Conclusions: Active lupus nephritis is associated with increased circulating syndecan-1 level, and thus may contribute towards the pathogenesis of cardiovascular complications in patients with lupus nephritis.