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 language | English (US) |
|---|---|
| Pages (from-to) | 1-13 |
| Number of pages | 13 |
| Journal | Pediatric Nephrology |
| DOIs | |
| State | Accepted/In press - Sep 3 2016 |
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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 journal › Article
}
TY - JOUR
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.
KW - BILAG
KW - Glomerulonephritis
KW - Lupus nephritis
KW - Systemic lupus erythematosus
KW - Urine biomarkers
UR - http://www.scopus.com/inward/record.url?scp=84984908120&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84984908120&partnerID=8YFLogxK
U2 - 10.1007/s00467-016-3485-3
DO - 10.1007/s00467-016-3485-3
M3 - Article
C2 - 27590021
AN - SCOPUS:84984908120
SP - 1
EP - 13
JO - Pediatric Nephrology
JF - Pediatric Nephrology
SN - 0931-041X
ER -