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A panel of urinary proteins predicts active lupus nephritis and response to rituximab treatment.
OBJECTIVES: âŒ30% of patients with SLE develop LN. Presence and/or severity of LN are currently assessed by renal biopsy, but biomarkers in serum or urine samples may provide an avenue for non-invasive routine testing. We aimed to validate a urinary protein panel for its ability to predict active renal involvement in SLE. METHODS: A total of 197 SLE patients and 48 healthy controls were recruited, and urine samples collected. Seventy-five of the SLE patients had active LN and 104 had no or inactive renal disease. Concentrations of lipocalin-like prostaglandin D synthase (LPGDS), transferrin, alpha-1-acid glycoprotein (AGP-1), ceruloplasmin, monocyte chemoattractant protein 1 (MCP-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were quantified by MILLIPLEXÂź Assays using the MAGPIX Luminex platform. Binary logistic regression was conducted to examine whether proteins levels associate with active renal involvement and/or response to rituximab treatment. RESULTS: Urine levels of transferrin (P <0.005), AGP-1 (P <0.0001), MCP-1 (P <0.001) and sVCAM-1 (P <0.005) were significantly higher in SLE patients when compared with healthy controls. Furthermore, levels of transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 (all P <0.0001) were higher in SLE patients with active LN when compared with patients without active LN. A combination of five urine proteins, namely LPGDS, transferrin, ceruloplasmin, MCP-1 and sVCAM-1 was a good predictor of active LN (AUC 0.898). A combined model of LPGDS, transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 predicted response to rituximab treatment at 12âmonths (AUC 0.818). CONCLUSIONS: Findings support the use of a urinary protein panel to identify active LN and potentially predict response to treatment with rituximab in adult SLE patients. Prospective studies are required to confirm findings.This work was funded by the Medical Research Council, grant MR/M01665X/1 âMaximizing SLE Therapeutic Potential by Application of Novel and Systemic Approaches and the Engineeringâ (MASTERPLANS). BILAG BR has been funded by unrestricted educational donations from Roche, GSK and LUPUS UK. This work was supported by the UKâs Experimental Arthritis Treatment Centre for Children (supported by Versus Arthritis #20621, Alder Hey Childrenâs NHS Foundation Trust, Alder Hey Childrenâs Charity, and the University of Liverpool) and supported also by the National Institute for Health Research (NIHR) Alder
Hey Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health