International validation of a urinary biomarker panel for identification of active lupus nephritis in children

Eve Mary Dorothy Smith, Andrea Lyn Jorgensen, Angela Midgley, Louise Oni, Beatrice Goilav, Chaim Putterman, Dawn Wahezi, Tamar Rubinstein, Diana Ekdawy, Rachel Corkhill, Caroline Ann Jones, Stephen David Marks, Paul Newland, Clarissa Pilkington, Kjell Tullus, Michael William Beresford

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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). Conclusion: In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an ‘excellent’ ability for accurately identifying active LN in children.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalPediatric Nephrology
DOIs
StateAccepted/In press - Sep 3 2016

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Lupus Nephritis
prostaglandin R2 D-isomerase
Biomarkers
Ceruloplasmin
Systemic Lupus Erythematosus
Transferrin
Area Under Curve
Glycoproteins
Vascular Cell Adhesion Molecule-1
Chemokine CCL2
Acids
Urine
Lipocalins
Orosomucoid
Nephritis
ROC Curve
Cohort Studies
Cross-Sectional Studies
Logistic Models

Keywords

  • BILAG
  • Glomerulonephritis
  • Lupus nephritis
  • Systemic lupus erythematosus
  • Urine biomarkers

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

International validation of a urinary biomarker panel for identification of active lupus nephritis in children. / Smith, Eve Mary Dorothy; Jorgensen, Andrea Lyn; Midgley, Angela; Oni, Louise; Goilav, Beatrice; Putterman, Chaim; Wahezi, Dawn; Rubinstein, Tamar; Ekdawy, Diana; Corkhill, Rachel; Jones, Caroline Ann; Marks, Stephen David; Newland, Paul; Pilkington, Clarissa; Tullus, Kjell; Beresford, Michael William.

In: Pediatric Nephrology, 03.09.2016, p. 1-13.

Research output: Contribution to journalArticle

Smith, EMD, Jorgensen, AL, Midgley, A, Oni, L, Goilav, B, Putterman, C, Wahezi, D, Rubinstein, T, Ekdawy, D, Corkhill, R, Jones, CA, Marks, SD, Newland, P, Pilkington, C, Tullus, K & Beresford, MW 2016, 'International validation of a urinary biomarker panel for identification of active lupus nephritis in children', Pediatric Nephrology, pp. 1-13. https://doi.org/10.1007/s00467-016-3485-3
Smith, Eve Mary Dorothy ; Jorgensen, Andrea Lyn ; Midgley, Angela ; Oni, Louise ; Goilav, Beatrice ; Putterman, Chaim ; Wahezi, Dawn ; Rubinstein, Tamar ; Ekdawy, Diana ; Corkhill, Rachel ; Jones, Caroline Ann ; Marks, Stephen David ; Newland, Paul ; Pilkington, Clarissa ; Tullus, Kjell ; Beresford, Michael William. / International validation of a urinary biomarker panel for identification of active lupus nephritis in children. In: Pediatric Nephrology. 2016 ; pp. 1-13.
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abstract = "Background: 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. Methods: 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. Results: 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). Conclusion: In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an ‘excellent’ ability for accurately identifying active LN in children.",
keywords = "BILAG, Glomerulonephritis, Lupus nephritis, Systemic lupus erythematosus, Urine biomarkers",
author = "Smith, {Eve Mary Dorothy} and Jorgensen, {Andrea Lyn} and Angela Midgley and Louise Oni and Beatrice Goilav and Chaim Putterman and Dawn Wahezi and Tamar Rubinstein and Diana Ekdawy and Rachel Corkhill and Jones, {Caroline Ann} and Marks, {Stephen David} and Paul Newland and Clarissa Pilkington and Kjell Tullus and Beresford, {Michael William}",
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T1 - International validation of a urinary biomarker panel for identification of active lupus nephritis in children

AU - Smith, Eve Mary Dorothy

AU - Jorgensen, Andrea Lyn

AU - Midgley, Angela

AU - Oni, Louise

AU - Goilav, Beatrice

AU - Putterman, Chaim

AU - Wahezi, Dawn

AU - Rubinstein, Tamar

AU - Ekdawy, Diana

AU - Corkhill, Rachel

AU - Jones, Caroline Ann

AU - Marks, Stephen David

AU - Newland, Paul

AU - Pilkington, Clarissa

AU - Tullus, Kjell

AU - Beresford, Michael William

PY - 2016/9/3

Y1 - 2016/9/3

N2 - Background: 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. Methods: 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. Results: 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). Conclusion: In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an ‘excellent’ ability for accurately identifying active LN in children.

AB - Background: 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. Methods: 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. Results: 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). Conclusion: In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an ‘excellent’ ability for accurately identifying active LN in children.

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KW - Glomerulonephritis

KW - Lupus nephritis

KW - Systemic lupus erythematosus

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