AB0412 URINARY SOLUBLE VCAM-1 IS A USEFUL BIOMARKER OF DISEASE ACTIVITY AND TREATMENT RESPONSE IN LUPUS NEPHRITIS
Authors: A. A. Gasparin, N. Pamplona Bueno de Andrade, V. Hax, P. Palominos, M. Siebert, R. Marx, P. Shaefer, F. Veríssimo Veronese, O. Monticielo
Journal: Annals of the Rheumatic Diseases (2020)

Background: The traditional lupus nephritis (LN) biomarkers are not sensitive nor specific enough for detecting ongoing disease activity and early relapse of nephritis and they do not reflect kidney damage nor have prognostic value 1 . Urinary biomarkers are directly excreted by the kidney and are easily obtained. They can also differentiate the renal activity of the disease from other organic manifestations more accurately than the serum biomarkers 2 . Vascular cell adhesion molecule-1 (VCAM-1) is involved in the progression of glomerular and tubulointerstitial injury in LN and its soluble form can be easily assessed in urine (uVCAM-1) 3 . Several studies correlated the uVCAM-1 levels with urine protein-creatinine ratio (UPC), with general disease activity and with active LN 3 . Objectives: To assess uVCAM-1 as a biomarker of disease activity and treatment response in LN. Methods: This prospective study enrolled patients with class III, IV or V LN diagnosed within the last three years and divided them in two groups: with and without active nephritis at the inclusion. The patients with active nephritis were included before they started a new immunosuppressive treatment. Active LN was defined as proteinuria (UPC≥0.5) plus active urinary sediment (hematuria, leukocyturia or cellular hematic/granular casts). At each visit, a urine sample was collected for uVCAM-1 evaluation and the nephritis status was accessed. Results: Median uVCAM-1 level was elevated in patients with active compared to inactive LN (p&lt;0.001). The ROC curve of uVCAM-1 demonstrated an AUC of 0.84 and a cutoff of 47.2 ng/mgCr yielded a good sensitivity (74.2%) and specificity (74.2%) for the diagnosis of active LN. A significant correlation was found between uVCAM-1 level and renal activity scores and traditional biomarkers of LN (table 1). The level of uVCAM-1 dropped in patients with active LN who went into remission (p&lt;0.001), increased in patients who went into activity (p=0.002) and did not change in patients who remained inactive (p=0.797) (figure 1). The level of uVCAM-1 peaked during the flare of LN (p&lt;0.05) (figure 2). Table 1. Correlations between urinary soluble VCAM-1 and other LN biomarkers/disease scores LN biomarkers/disease scores VCAM-1 SLEDAI-2k 0.597*** Renal SLEDAI 0.569*** Renal SLAM-R 0.470*** Renal SLICC 0.620*** Anti-dsDNA 0.342** C3 -0.344** C4 -0.382** UPC 0.654*** Spearman’s correlation coefficients * p value &lt;0.05; ** p value &lt;0.01; *** p value &lt;0.001 C, complement; LN, lupus nephritis; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; renal SLAM-R, The renal Systemic Lupus Activity Measure revised; renal SLICC, The Systemic Lupus International Collaborating Clinics renal activity/response exercise; UPC, urine protein-creatinine ratio. Conclusion: The uVCAM-1 is a reliable biomarker that reflects renal disease activity and is useful for monitoring individual patients with lupus nephritis over time. References: [1] Mok CC. Biomarkers for lupus nephritis: A critical appraisal. J Biomed Biotechnol. 2010;2010:638413. [2] Reyes-Thomas J, Blanco I, Putterman C. Urinary Biomarkers in Lupus Nephritis. Clin Rev Allergy Immunol. 2010;40:138–50. [3] Gasparin AA, Pamplona Bueno de Andrade N, Hax V, Tres GL, Veronese FV, Monticielo OA. Urinary biomarkers for lupus nephritis: the role of the vascular cell adhesion molecule-1. Lupus. 2019;28:265-272. Acknowledgments: We acknowledge the Research Incentive Fund (FIPE/HCPA) and the Research Support Fund of Brazilian Society of Rheumatology that supported this work. Disclosure of Interests: Andrese Aline Gasparin: None declared, Nicole Pamplona Bueno de Andrade: None declared, Vanessa Hax: None declared, Penelope Palominos Grant/research support from: This work was sponsored by the regional society of rheumatology (Sociedade de Reumatologia do Rio Grande do Sul)., Marina Siebert: None declared, Romulo Marx: None declared, Pedro Shaefer: None declared, Francisco Veríssimo Veronese: None declared, Odirlei Monticielo: None declared