Background Juvenile-onset Systemic Lupus Erythematous (JSLE) is a complex autoimmune condition, affecting the kidneys in up to 80% of cases (Lupus Nephritis (LN)) . Renal histology is currently the gold standard for diagnosis and monitoring LN. Conventional markers fail to adequately track LN disease activity over time. Urinary Vascular Cell Adhesion Molecule-1 (VCAM-1) has been shown to cross-sectionally differentiate between adult SLE patients with active LN and inactive LN , but has not been assessed longitudinally.
Objectives To assess whether urinary VCAM-1 can predict changes in the LN disease activity longitudinally.
Methods Urinary concentration of VCAM-1 was quantified by enzyme-linked immunosorbent assay in JSLE patients participating in the UK JSLE Cohort Study. Patients were aged <16 years at the time of diagnosis. LN disease activity was defined using the renal domain of the British Isles Lupus Assessment Group (r-BILAG). Active LN patients had a r-BILAG score of A/B plus previous histological confirmation, whereas inactive LN patients had a r-BILAG score of D/E. Depending on the change in r-BILAG the patient was classified as having improved, stable or worsened LN. Multinomial regression analysis was used to assess the percentage change in biomarker concentrations between groups, correcting for multiple patient visits. Binary logistic regression modelling and receiver-operating curve (ROC curve) analysis assessed the ability of VCAM-1 to predict LN disease activity at future time points.
Results 58 JSLE patients were recruited to this study and followed over a median of 2.3 clinic visits [Interquartile range (IQR) 1.6-2.8]. 66% had stable disease, 10% had persistently active LN and 24% fluctuated between active and inactive LN. Median VCAM-1 levels were significantly different between patients with persistently active LN (29.5pg/mgCr [IQR 9.2-91.2]) and persistently inactive LN (4.3pg/mgCr [IQR 1.2-15.3] (p<0.001)). Multinomial regression showed a significant difference in VCAM-1 depending on whether a patient's LN worsened, improved or remained stable over time (p=0.028). Urinary VCAM-1 level below 8.98pg/mgCr predicted an improvement in renal disease activity (sensitivity 76%, specificity 77% and an area under the curve =0.895).
Conclusions Our work has shown that urinary VCAM-1 levels differentiate between JSLE patients with worsened, improved or stable LN disease activity over time, representing a good predictor of LN improvement. It is anticipated that biomarker led monitoring and treatment will improve future LN management and outcomes.
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Howe HS, Kong KO, Thong BY, et al. Urine sVCAM-1 and sICAM-1 levels are elevated in lupus nephritis. Int J Rheum Dis 2012;15(1):13-6.
Disclosure of Interest None declared