Urinary soluble VCAM-1 is a useful biomarker of disease activity and treatment response in lupus nephritis

Abstract

Introduction: Vascular cell adhesion molecule-1 (VCAM-1) is involved in the progression of glomerular and tubulointerstitial injury in lupus nephritis (LN) and can be easily assessed in urine. The aim of this study was to assess urinary soluble VCAM-1 (uVCAM-1) as a biomarker of disease activity and treatment response in LN.

Methods: This prospective study enrolled 62 patients with class III, IV or V LN diagnosed within the last 3 years and divided them in two groups: with and without active nephritis at the inclusion, each group with 31 patients. At each visit, a urine sample was collected for uVCAM-1 evaluation and the nephritis status was assessed.

Results: Median uVCAM-1 level was elevated in patients with active compared to inactive LN (P < 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. The level of uVCAM-1 dropped in patients with active LN who went into remission (P < 0.001), increased in patients who went into activity (P = 0.002) and did not change in patients who remained inactive (P = 0.797). The level of uVCAM-1 peaked during the flare of LN (P < 0.05).

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.

Keywords: Lupus nephritis; Urinary biomarker; VCAM-1; Vascular cell adhesion molecule-1.

Fig. 1

Urinary VCAM-1 analysis according to nephritis status during follow-up. Active LN was defined as proteinuria (UPCR ≥0.5) plus active urinary sediment. Complete renal response was defined as UPCR < 0.5 and normal or near normal [within 10% of normal eGFR if previously abnormal] eGFR. Partial renal response was defined as ≥50% reduction in proteinuria to subnephrotic levels and normal or near-normal eGFR. eGFR: estimated glomerular filtration rate; UPCR: urine protein-creatinine ratio

Fig. 2

Urinary soluble VCAM-1 levels according to lupus nephritis status. Active LN was defined as proteinuria (UPCR ≥0.5) plus active urinary sediment (hematuria, leukocyturia or cellular hematic/granular casts). LN: lupus nephritis; UPCR: urine protein-creatinine ratio

Fig. 3

uVCAM-1 (a), C3 (b), C4 (c), anti-dsDNA (d), UPCR (e) levels at different time points relative to a lupus nephritis flare. The x-axis represents time (in months). The levels were evaluated 8 and 4 months before and after a flare, including at the time of the flare itself (time point 0). The number of patients who contributed at each moment was informed in uVCAM-1 (a) and is the same for (b), (c), (d) and (e). Graph represents median and interquartile range. *P < 0.05 compared with level at flare. uVCAM-1: urinary vascular cell adhesion molecule 1