Vascular biomarkers in patients with lupus nephritis

Lupus nephritis is an important, but reversible, cause of renal failure especially in Asia where it shows a higher incidence rate when compared with other parts of the world. Lupus patients also show an increased incidence of vascular complications. Over the past two decades improvement in immunosuppressive treatment for severe lupus nephritis have markedly reduced short-term mortality, and death due to vascular disease has emerged as an important cause of mortality during long-term follow-up. There are data demonstrating a relationship between systemic inflammation and vascular injury. However, this has not been fully defined in patients with lupus nephritis. The natural course of lupus nephritis is characterized by intermittent flares separated by long periods of disease quiescence. Whether there is any serial change in the biomarkers of vascular injury and inflammation with disease activity has not been elucidated. This study investigated the levels of IL-6, IL-10, IL-12, syndecan-1, thrombomodulin, sICAM-1, VCAM-1, E-selectin, decorin and hyaluronan in archived serum samples from 29 patients with biopsy-proven diffuse proliferative lupus nephritis, and their relationship with disease activity and clinical and serological parameters of disease. Serial serum samples obtained at intervals of 3-4 months over a minimum of 24 months were selected from the same patients for longitudinal studies. Single serum samples from age- and sex-matched patients with IgA nephropathy and healthy subjects were included as renal disease controls and healthy controls respectively. Serum syndecan-1, thrombomodulin, VCAM-1, hyaluronan and decorin, but not sICAM-1 and E-selectin levels were significantly higher in lupus nephritis patients when compared to corresponding serum levels in patients with IgA nephropathy or healthy individuals. Serum syndecan-1, thrombomodulin, VCAM-1 and hyaluronan levels showed a temporal relationship with disease activity and anti-dsDNA antibodies, and correlated with SLEDAI, proteinuria and serum creatinine levels, and inversely correlated with serum C3, C4 and albumin levels. Serum decorin and sICAM-1 levels correlated with proteinuria but not with anti-dsDNA antibody level. Serum E-selectin level showed no correlation with clinical or serological parameters of disease. Serum levels of IL-6, IL-10 and IL-12 could not be detected in this study. Serum syndecan-1, VCAM-1 and HA levels distinguished patients with active lupus nephritis from healthy subjects and patients with IgA nephropathy. Serum thrombomodulin level distinguished between patients with lupus nephritis and healthy subjects, but not patients with IgA nephropathy. Serum decorin, sICAM-1 and E-selectin could not distinguish between patients with renal disease and healthy subjects. Our data suggest that biomarkers of inflammation and vascular injury are increased in lupus nephritis patients when compared to controls, and may suggest subclinical vascular damage. Whether measurement of these biomarkers can be used to identify lupus patients at risk of developing vascular injury warrants further investigation.published_or_final_versionMedicineMasterMaster of Research in Medicin