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

18 Scopus citations

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)283-295
Number of pages13
JournalPediatric Nephrology
Volume32
Issue number2
DOIs
StatePublished - Feb 1 2017

Keywords

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

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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    Smith, E. M. D., Jorgensen, A. L., Midgley, A., Oni, L., Goilav, B., Putterman, C., Wahezi, D., Rubinstein, T., Ekdawy, D., Corkhill, R., Jones, C. A., Marks, S. D., Newland, P., Pilkington, C., Tullus, K., & Beresford, M. W. (2017). International validation of a urinary biomarker panel for identification of active lupus nephritis in children. Pediatric Nephrology, 32(2), 283-295. https://doi.org/10.1007/s00467-016-3485-3