Urinary VCAM-1, KIM-1, and ET-1 as Biomarkers of Lupus Nephritis: Correlation with Immunological Parameters in Hospital USM

Abstract

Introduction: So far, there is no conventional parameters that have been proven to possess the ability to predict the histology of systemic lupus erythematosus (SLE). A few autoimmune serology markers of SLE including anti-dsDNA antibodies, complement C3 and C4, and anti-nucleosome could be helpful clinically, but the correlation between those and lupus renal disease is still imperfect. Recently, the urinary vascular cell adhesion molecule-1 (VCAM-1), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) have been studied for the diagnosis of lupus nephritis (LN). Nevertheless, it is still unknown whether the urinary VCAM-1, KIM-1 and ET-1 could be used as disease monitoring and flare predictor tools for LN.Objective: To evaluate the levels of VCAM-1, KIM-1, and ET-1 in active LN, inactive LN and controls, cut-off points and diagnostic accuracy and their correlation with SLE Disease Activity Index (SLEDAI), renal SLEDAI (rSLEDAI), and the standard immunological markers.Methods: This study involved 60 LN patients and 30 controls conducted in the Hospital Universiti Sains Malaysia (Hospital USM) from September 2016 to February 2018. All three biomarkers were determined by enzyme-linked immunosorbent assay (ELISA) in urine samples of patients. Receiver operating characteristic analysis was performed to obtain the best cut-off values and to calculate the performance of these markers. The correlation was done between urinary biomarkers and immunological parameters. Statistical analysis was performed using SPSS software, version 22.0.Results: Urinary VCAM-1, KIM-1, and ET-1 levels were significantly higher in active LN patients compared to inactive LN patients and controls. These markers correlated significantly with anti-dsDNA, complement C3, complement C4, urine protein/urine creatinine (Uprot/Ucreat), SLE disease activity index (SLEDAI), and renal SLEDAI scores. The urinary KIM-1 significantly correlated with all the immunological parameters except for complement C4. Urinary ET-1 showed higher specificity and sensitivity in differentiating LN patients and healthy controls (AUC 0.809) than urinary VCAM-1 (AUC 0.725) and urinary KIM-1 (AUC 0.640). Conclusions:Our study demonstrated that urinary VCAM-1, KIM-1, and ET-1 might be potential biomarkers specific for the lupus renal disease.