Serum VCAM-1 level in patients with lupus nephritis and its clinical associations

Abstract

Background: Cardiovascular disease is more common in patients with lupus nephritis. Endothelial cell activation or injury is associated with shedding of adhesion molecules into the circulation. We investigated circulating VCAM-1 level in lupus nephritis patients and its clinical associations. Methods: Archived paired serum samples, one during flare and the other during clinical remission, from 29 patients with biopsy-proven Class III/IV lupus nephritis were included. Serial samples obtained at intervals of 3-4 months over two years in 27 stable patients were included for longitudinal studies. Smokers and patients with serum creatinine above 450μmol/l or eGFR below 15ml/min were excluded. Age- and sexmatched patients with non-lupus glomerular diseases and healthy subjects (n=25 for each group) were included as controls. Serum VCAM-1 level was measured by ELISA. Results: 482 serum samples from lupus nephritis patients (20 females and 9 males; age 39.0±10.2 years; disease duration 7.6±8.6 years) were studied. Only one patient had clinically evident vascular disease. Serum VCAM-1 level was significantly higher during active lupus nephritis, compared to remission samples, patients with non-lupus renal diseases or healthy subjects (P<0.001, for all). VCAM-1 level correlated with SLEDAI and the level of anti-dsDNA antibody, serum creatinine, urine albumin-to-creatinine ratio, and prevailing prednisolone daily dose, and inversely correlated with serum C3 and albumin levels. VCAM-1 level was not associated with lipid parameters. Longitudinal studies showed that increased circulating VCAM-1 level preceded clinically evident renal flare by 4.6±3.4 months, and persisted for 11.7±8.8 months after clinical disease quiescence. Analysis with ROC curve showed that serum VCAM-1 level distinguished patients with active lupus nephritis from healthy subjects with sensitivity and specificity rates of 96.5% and 96.0% respectively (P<0.0001), and from patients with non-lupus renal diseases with sensitivity and specificity rates of 89.6% and 82.6% respectively (P<0.0001). Conclusions: Active lupus nephritis was associated with elevated VCAM-1 level in serum, which persisted for many months despite renal response after treatment. The findings suggest prolonged subclinical vascular endothelial injury and could have implications on the pathogenesis of cardiovascular complications.