Urinary Vascular Cell Adhesion Molecule, But Not Neutrophil Gelatinase-associated Lipocalin, Is Associated with Lupus Nephritis

Abstract

Objective Vascular cell adhesion molecule-1 (VCAM-1), an adhesion molecule, is involved in the progression of glomerular and tubulointerstitial injury. Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin superfamily, has been shown to rise in both acute and chronic kidney damage. Both VCAM-1 and NGAL have been found at high levels in the urine of patients with active lupus nephritis. We investigated both as potential biomarkers for lupus nephritis. Methods VCAM-1 and NGAL were measured by ELISA during 1 to 8 clinic visits in 107 patients with systemic lupus erythematosus (SLE; 91% women, 51% black, 36% white, 4% Asian, 4% Hispanic, and 5% others) for a total of 190 visits. Patients’ mean age was 41 years. We analyzed the relationship between these potential urine biomarkers and the urine protein/creatinine ratio (urine Pr/Cr), the Systemic Lupus International Collaborating Clinics (SLICC) renal activity score, SLE Disease Activity Index renal descriptors, and other clinical variables. Results VCAM-1 levels were strongly associated with the physician’s global estimate of disease activity (p = 0.0002), the renal visual analog scale (p < 0.0001), the urine Pr/Cr (p < 0.0001), and SLICC renal activity score (p < 0.0001). VCAM-1 levels were also associated with a urine Pr/Cr ≥ 0.5 (p < 0.0001). NGAL was not associated with any measure of disease activity or with lupus serologies. Conclusion Urine VCAM-1 had a strong association with measures of disease activity, including multiple renal activity descriptors. In contrast to previous SLE studies, NGAL failed to show any association with lupus nephritis.

Urine angiostatin and VCAM‐1 surpass conventional metrics in predicting elevated renal pathology activity indices in lupus nephritis

“…It also functions in leukocyte‐endothelial cell signal transduction, and plays a role in the development of atherosclerosis and various autoimmune diseases, including SLE, rheumatoid arthritis, Sjögren's syndrome and vasculitis . Several studies have reported that serum and urinary VCAM‐1 correlate significantly with overall disease activity and damage scores in SLE, as well as with LN . It is also a good marker of renal disease in murine lupus …”

“…It also functions in leukocyte‐endothelial cell signal transduction, and plays a role in the development of atherosclerosis and various autoimmune diseases . Many studies have suggested that serum and urinary levels of soluble VCAM‐1 significantly correlate with overall disease activity and damage scores in SLE, as well as with LN . Our previous study documented that urinary VCAM‐1 was increased in SLE patients, and correlated with renal activity and SLE Disease Activity Index (SLEDAI) scores …”

“…12,13 Many studies have suggested that serum and urinary levels of soluble VCAM-1 significantly correlate with overall disease activity and damage scores in SLE, as well as with LN. [14][15][16][17][18][19] Our previous study documented that urinary VCAM-1 was increased in SLE patients, and correlated with renal activity and SLE Disease Activity Index (SLEDAI) scores. 19 Currently, the relationship of these urinary biomarkers to specific histologic features of LN in concurrent renal biopsies is poorly understood, and has not been systematically examined.…”

International validation of a urinary biomarker panel for identification of active lupus nephritis in children

“…Urinary NGAL has previously been shown to be a useful predictor of impending flare in both the UK JSLE Cohort [26] and in an adult SLE study of the ELC which included a University College London validation cohort [43]. Kiani et al were also unable to detect an association between urinary NGAL and LN in a prospective study that included 107 adult SLE patients [44]. These observations may be due to urinary NGAL levels peaking before flares and then receding before the event becomes clinically detectable [45].…”

Biomarkers and Updates on Pediatrics Lupus Nephritis

“…121 VCAM-1 plays a role in tethering leukocytes, which are drawn to sites of inflammation, to endothelial cells. 122 Urinary VCAM-1 has been shown in several studies of human disease to be strongly correlated with LN activity and severity 77,123,124 in LN. Serum levels of VCAM have previously been shown to correlate with the severity of LN, being highest in WHO Class III and IV, versus inactive or mild nephritis (WHO Class I or II), 125 and levels diminished with treatment.…”