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
N1 - Funding Information:
This work was supported by the Alder Hey Children’s Kidney Fund through a training fellowship [UOG10065 to ES]. Lupus UK also provides financial support for co-ordination of the UK JSLE Cohort Study. TR is supported by the Lupus Foundation of America Career Development Award, and the NIH (National Institutes of Health) Loan Repayment Program for Pediatric Research. BG is supported by the Children’s Hospital at Montefiore Young Investigator Award. CP and BG are supported by NIH/NCI 1U19CA179564 and NIH/NCI 1UH2/3TR000933.
Funding Information:
The authors would like to acknowledge all patients and their families for participating in this study, as well as all the support given by the entire multi-disciplinary team within each of the paediatric centres. The study was supported by the National Institute of Health Research (NIHR) Clinical Research Network (CRN), with special thanks to all children and CRN Research Nurses and staff in both centres, the NIHR Alder Hey Clinical Research Facility for Experimental Medicine and all those who have supported the work of the UK JSLE Study Group to date. Specific acknowledgement goes to the clinical teams, consultants, research nurses and clinical nurse specialists in each centre, including: Yvonne Glackin, Olivia Lloyd, Susan Wadeson and Collette Hodgson. Special recognition also goes to Dr. Duncan Appleby for database and information technology support, Graham Jeffers for laboratory support, Carla Roberts for co-ordination of the UK JSLE Cohort study and Nicole Jordan for co-ordination of the Einstein Lupus Cohort.
Publisher Copyright:
© 2016, The Author(s).
PY - 2017/2/1
Y1 - 2017/2/1
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
VL - 32
SP - 283
EP - 295
JO - Pediatric Nephrology
JF - Pediatric Nephrology
SN - 0931-041X
IS - 2
ER -