Background/Purpose: The goal of this study is to investigate how urinary angiostatin, VCAM-1 and established measures of renal function relate to specific histologic findings in paired kidney biopsy samples from patients with lupus nephritis (LN).

Methods: Patients fulfilling the ACR classification for SLE were recruited into the study. Urine samples were collected from 54 lupus nephritis patients together with concurrent kidney biopsy samples and examined for urinary angiostatin and vascular cell adhesion molecule 1 (VCAM-1) protein levels. SLE disease activity was assessed using the SLEDAI, renal disease activity was assessed by the renal SLEDAI (range 0-16; 0= inactive LN, ≥ 8= active renal). The ISN/RPS criteria were used to assess the histologic features of LN. Our patients were categorized into two groups; active proliferative (ISN/RPS classes III/IV) and non-proliferative (classes I/II/V). Biopsy activity and chronicity indices (BAI, BCI respectively) were used for biopsy assessment according to the standards of NIH for LN, the BAI score (range 0-24; 0= inactive LN) and BCI score (range 0-12; 0= no LN chronicity), with BAI and BCI scores of ≥7 and ≥4 respectively considered as risk factors for poor LN outcomes. Nonparametric tests were used to examine the association of both urinary biomarkers and established traditional laboratory markers of renal function with nine specific renal histologic features seen in LN using concurrent renal biopsies.

Results: 54 active LN patients (94.4% women, age 33.3±9.7 years) and 20 healthy controls were studied. Unlike conventional laboratory measures, urinary angiostatin and VCAM-1 levels normalized to Cr were significantly higher in patients with active proliferative LN than non-proliferative LN (angiostatin 21900±3.43 vs 2200±0.79 pg/ng; P<0.0001; VCAM-1 1249±3.93 vs 166±42.5 pg/ng; P<0.0001). A significant correlation was found between urine VCAM-1 and SLEDAI (r = 0.324, P <0.05), as well as renal SLEDAI (r = 0.319, P <0.05). Urinary angiostatin correlated significantly with renal SLEDAI (r = 0.327, P < 0.05). Urinary angiostatin and VCAM-1 strongly correlated with the renal biopsy activity index in concurrent biopsies (r = 0.929, P < 0.001 and r = 0.97, P < 0.001 respectively), but not with the chronicity index. Both angiostatin and VCAM-1 showed an outstanding ability (AUC 0.97, 0.98 respectively) to predict concurrent renal biopsy activity index score ≥ 7, compared to conventional measures such as sCr, eGFR and uPCR. Whereas urine VCAM-1 was most significantly associated with fibrous crescents, urine angiostatin was most significantly associated with endocapillary proliferation, cellular crescents, fibrinoid necrosis and fibrous crescents in concurrent renal biopsies.

Conclusion: Urinary angiostatin and VCAM-1 are associated with specific histologic features of LN activity and chronicity in concurrent renal biopsies. Further longitudinal studies are necessary to delineate the utility of these two urinary proteins in tracking renal pathology changes in SLE patients, and predicting long-term patient and renal mortality in LN.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/urine-angiostatin-and-vcam-1-surpass-conventional-metrics-in-predicting-elevated-renal-pathology-activity-indices-in-lupus-nephritis/