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Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis

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Abstract

We hypothesized that neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of disease activity in lupus nephritis. NGAL in serial plasma (PNGAL) and urine (UNGAL) samples was measured by enzyme-linked immunosorbent assay (ELISA) in 85 participants with pediatric systemic lupus erythematosus (pSLE), healthy children (n = 50), and children with juvenile idiopathic arthritis (JIA) (n = 30). Disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Plasma and urinary NGAL were significantly increased in subjects with pSLE compared with those with JIA or with healthy controls (all p < 0.03), and unrelated to subjects’ age, weight, or height. Plasma and urinary NGAL were stable in pSLE subjects with unchanged disease activity. The pSLE subjects with worsening global or renal disease activity had a mean ± standard error (SE) increase of UNGAL (in ng/ml) of 11.5 ± 6.4 or 36.6 ± 12.1 (p < 0.01), corresponding to a 156% or 380% increase, respectively. PNGAL increased with worsening disease but to a much lesser degree than UNGAL [global disease activity (mean ± SE): 7.3 ± 6.2 or 21%; renal disease activity: 20.2 ± 6.0 or 51%; both p = not significant]. In conclusion, NGAL in urine but not in plasma represents a novel biomarker for renal disease activity in pSLE.

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Acknowledgements

This study is supported by clinical research grant NIAMS P60 AR47784. Dr. Brunner is supported by a grant from the Alliance for Lupus Research and the CCHMC Translational Research Initiative. Dr. Devarajan is supported by grants from the NIH/NIDDK (RO1 DK53289, P50 DK52612, R21 DK060163). Dr. Wiers is supported by T32 AR007594 and the NIH Loan Repayment Program. We are indebted to our clinical coordinators Jamie Meyer-Eaton and Shannen Nelson for their assistance, Lukasz Itert for the data management, the NIAMS Tissue Repository (director: Susan Thompson; AR047363) for the sample management, Qing Ma for her technological support, and to our patients and families for their participation.

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Michiko Suzuki & Prasad Devarajan

  2. William Rowe Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, E 4010, 3333 Burnet Avenue, Cincinnati, OH, 45229-3039, USA

    Kristina M. Wiers, Murray H. Passo & Hermine I. Brunner

  3. Division of Rheumatology, Children’s Memorial Hospital, Northwestern University, Chicago, IL, USA

    Marisa S. Klein-Gitelman

  4. Pediatric Immunology, Division of Pediatric Rheumatology and Immunology, Hackensack University Medical Center, Hackensack, NJ, USA

    Kathleen A. Haines

  5. Medical College of Wisconsin, and Children’s Research Institute, Milwaukee, WI, USA

    Judyann Olson

  6. Division of Pediatric Rheumatology, University of Chicago La Rabida Children’s Hospital, Chicago, IL, USA

    Karen B. Onel

  7. Department of Pediatrics, Oklahoma University Health Science Center, Oklahoma City, OK, USA

    Kathleen O’Neil

  8. Department of Pediatrics and Internal Medicine, Rainbow Babies & Children’s Hospital, University Hospitals/Case Medical Center, Cleveland, OH, USA

    Nora G. Singer

  9. Department of Pediatrics, British Columbia Children’s Hospital, Vancouver, BC, Canada

    Lori Tucker

  10. Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    Jun Ying

Authors
  1. Michiko Suzuki
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  2. Kristina M. Wiers
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  3. Marisa S. Klein-Gitelman
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  4. Kathleen A. Haines
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  5. Judyann Olson
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  6. Karen B. Onel
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  7. Kathleen O’Neil
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  8. Murray H. Passo
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  9. Nora G. Singer
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  10. Lori Tucker
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  11. Jun Ying
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  12. Prasad Devarajan
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  13. Hermine I. Brunner
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Correspondence to Hermine I. Brunner.

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Suzuki, M., Wiers, K.M., Klein-Gitelman, M.S. et al. Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis. Pediatr Nephrol 23, 403–412 (2008). https://doi.org/10.1007/s00467-007-0685-x

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  • DOI: https://doi.org/10.1007/s00467-007-0685-x

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