Urine VCAM-1 as a marker of renal pathology activity index in lupus nephritis

Abstract

IntroductionAlthough renal pathology is highly predictive of the disease course in lupus nephritis, it cannot be performed serially because of its invasive nature and associated morbidity. The goal of this study is to investigate whether urinary levels of CXC ligand 16 (CXCL16), monocyte chemotactic protein-1 (MCP-1) or vascular cell adhesion molecule-1 (VCAM-1) in patients with lupus nephritis are predictive of particular features of renal pathology in renal biopsies obtained on the day of urine procurement.MethodsCXCL16, MCP-1, and VCAM-1 levels were measured in urine samples from 74 lupus nephritis patients and 13 healthy volunteers. Of the patients enrolled, 24 patients had a concomitant kidney biopsy performed at the time of urine collection. In addition, patients with other renal diatheses were also included as controls.ResultsAll three molecules were elevated in the urine of systemic lupus erythematosus patients, although VCAM-1 (area under curve = 0.92) and MCP-1 (area under curve = 0.87) were best at distinguishing the systemic lupus erythematosus samples from the healthy controls, and were also most strongly associated with clinical disease severity and active renal disease. For patients in whom concurrent renal biopsies had also been performed, urine VCAM-1 exhibited the strongest association with the renal pathology activity index and glomerulonephritis class IV, although it correlated negatively with the chronicity index. Interestingly, urinary VCAM-1 was also elevated in anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis, focal segmental glomerulosclerosis and membranous nephropathy but not in minimal-change disease.ConclusionUrinary VCAM-1 emerges as a reliable indicator of the activity:chronicity ratios that mark the underlying renal pathology in lupus nephritis. Since VCAM-1 is involved in the acute phase of inflammation when leukocytic infiltration is ongoing, longitudinal studies are warranted to establish whether tracking urine VCAM-1 levels may help monitor clinical and pathological disease activity over time.

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis

“…We then measured urinary angiostatin levels and compared them with the renal pathology activity index and the renal pathology chronicity index in these paired urine/ biopsy samples collected simultaneously. Renal pathology activity and chronicity indices were computed as described elsewhere (24,25). The activity index is based on evaluation of six histologic parameters (i.e.…”

Relationship between urinary protein changes in lupus nephritis and renal pathology

“…Urinary protein content is closely related with renal tubule pathological changes; increase in the urinary protein content is associated with a higher degree of renal tubular damage (Hiraki et al, 2012). This may be because renal tubules release lysosomes and complement protein after reabsorbing protein, while infiltrated renal tubular interstitial cells and inflammatory cells lead to renal tubular atrophy and mesenchymal transition (Jaybhaye et al, 2011;Romick-Rosendale et al, 2011;Singh et al, 2012;Takasaki, 2012;Yahata et al, 2012).…”

Loss of Immune Tolerance Is Controlled by ICOS in Sle1 Mice

“…8C, 8D). VCAM-1 is associated with the migration and recruitment of inflammatory cells, and vWF is associated with endothelial cell dysfunction (53)(54)(55). ICOS-deficient B6.Sle1 mice had reduced levels of vWF and VCAM-1, similar to wt B6 animals (Fig.…”