title: International validation of a urinary biomarker panel for identification of active lupus nephritis in children.
abstract: Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts.
  
  
  
  Novel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy.
  
  
  
  A total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (pc) < 0.05] across both cohorts. Urinary TF also differed between patient groups in Cohort 2 (pc= 0.001). Within Cohort 1, the optimal biomarker panel included AGP, ceruloplasmin, LPGDS and TF (AUC 0.920 for active LN identification). These results were validated in Cohort 2, with the same markers resulting in the optimal urine biomarker panel (AUC 0.991).
  
  
  
  In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an 'excellent' ability for accurately identifying active LN in children.
authors: Department of Women's and Children's Health, Institute of Translational Medicine, Institute of Child Health in the Park, Alder Hey Children's Hospital and University of Liverpool, Eaton Road, Liverpool, L12 2AP, UK. esmith8@liverpool.ac.uk.
authors: Eve Mary Dorothy
authors: EM
authors: Smith
authors: Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: Andrea Lyn
authors: AL
authors: Jorgensen
authors: Department of Women's and Children's Health, Institute of Translational Medicine, Institute of Child Health in the Park, Alder Hey Children's Hospital and University of Liverpool, Eaton Road, Liverpool, L12 2AP, UK.
authors: Angela
authors: A
authors: Midgley
authors: Department of Women's and Children's Health, Institute of Translational Medicine, Institute of Child Health in the Park, Alder Hey Children's Hospital and University of Liverpool, Eaton Road, Liverpool, L12 2AP, UK.
authors: Louise
authors: L
authors: Oni
authors: Division of Nephrology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA.
authors: Beatrice
authors: B
authors: Goilav
authors: Division of Rheumatology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
authors: Chaim
authors: C
authors: Putterman
authors: Division of Pediatric Rheumatology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA.
authors: Dawn
authors: D
authors: Wahezi
authors: Division of Pediatric Rheumatology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA.
authors: Tamar
authors: T
authors: Rubinstein
authors: Department of Women's and Children's Health, Institute of Translational Medicine, Institute of Child Health in the Park, Alder Hey Children's Hospital and University of Liverpool, Eaton Road, Liverpool, L12 2AP, UK.
authors: Diana
authors: D
authors: Ekdawy
authors: Department of Women's and Children's Health, Institute of Translational Medicine, Institute of Child Health in the Park, Alder Hey Children's Hospital and University of Liverpool, Eaton Road, Liverpool, L12 2AP, UK.
authors: Rachel
authors: R
authors: Corkhill
authors: Department of Paediatric Nephrology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors: Caroline Ann
authors: CA
authors: Jones
authors: Department of Paediatric Nephrology, Great Ormond Street Hospital, London, UK.
authors: Stephen David
authors: SD
authors: Marks
authors: Biochemistry Department, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors: Paul
authors: P
authors: Newland
authors: Department of Paediatric Rheumatology, Great Ormond Street Hospital, London, UK.
authors: Clarissa
authors: C
authors: Pilkington
authors: Department of Paediatric Nephrology, Great Ormond Street Hospital, London, UK.
authors: Kjell
authors: K
authors: Tullus
authors: Department of Women's and Children's Health, Institute of Translational Medicine, Institute of Child Health in the Park, Alder Hey Children's Hospital and University of Liverpool, Eaton Road, Liverpool, L12 2AP, UK.|Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors: Michael William
authors: MW
authors: Beresford
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D002570:Ceruloplasmin; D018932:Chemokine CCL2 / Q000652:urine; D002648:Child; D003430:Cross-Sectional Studies; D004739:England; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000652:urine; D000071068:Lipocalin-2 / Q000652:urine; D054834:Lipocalins / Q000652:urine; D016015:Logistic Models; D008181:Lupus Nephritis / Q000175:diagnosis* / Q000652:urine*; D008297:Male; D009961:Orosomucoid / Q000652:urine; D011237:Predictive Value of Tests; D012372:ROC Curve; D014481:United States; D019010:Vascular Cell Adhesion Molecule-1 / Q000652:urine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D000071068:Lipocalin-2; D054834:Lipocalins; D009961:Orosomucoid; D019010:Vascular Cell Adhesion Molecule-1; D002570:Ceruloplasmin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase
keywords: BILAG; Glomerulonephritis; Lupus nephritis; Systemic lupus erythematosus; Urine biomarkers