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Drs. Brunner and Devarajan are coinventors on patents covering biomarker panels for the diagnosis of lupus nephritis.
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Systemic Lupus Erythematosus
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Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis
Article first published online: 27 JUL 2012
DOI: 10.1002/art.34426
Copyright © 2012 by the American College of Rheumatology
Additional Information
How to Cite
Brunner, H. I., Bennett, M. R., Mina, R., Suzuki, M., Petri, M., Kiani, A. N., Pendl, J., Witte, D., Ying, J., Rovin, B. H. and Devarajan, P. (2012), Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis. Arthritis & Rheumatism, 64: 2687–2697. doi: 10.1002/art.34426
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Drs. Brunner and Devarajan are coinventors on patents covering biomarker panels for the diagnosis of lupus nephritis.
- ‡
Dr. Devarajan has received consulting fees, speaking fees, and/or honoraria from Abbott Diagnostics and Alere (less than $10,000 each) and is a coinventor on patent applications for the use of neutrophil gelatinase–associated lipocalin as a biomarker for acute kidney injury.
Publication History
- Issue published online: 27 JUL 2012
- Article first published online: 27 JUL 2012
- Accepted manuscript online: 10 FEB 2012 04:39PM EST
- Manuscript Accepted: 2 FEB 2012
- Manuscript Received: 23 MAY 2011
Funded by
- Alliance for Lupus Research
- Cincinnati Children's Hospital Medical Center Translational Research Initiative
- NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases). Grant Numbers: U01-AR-059509, P60-AR-47784
- Hopkins Lupus Cohort (NIH). Grant Number: AR-43727
- National Center for Research Resources. Grant Number: UL1-RR-025005
- NIH (National Institute of Diabetes and Digestive and Kidney Diseases). Grant Numbers: DK-074661, DK-077331, R01-DK53289
- Alliance for Lupus Research
- Cincinnati Children's Hospital Medical Center
- Department of Defense. Grant Number: PR064328
- NIH. Grant Number: P30-AR-047363
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Abstract
Objective
To investigate the relationship of urinary biomarkers and established measures of renal function to histologic findings in lupus nephritis (LN), and to test whether certain combinations of the above-mentioned laboratory measures are diagnostic for specific histologic features of LN.
Methods
Urine samples from 76 patients were collected within 2 months of kidney biopsy and assayed for the urinary biomarkers lipocalin-like prostaglandin D synthase (L-PGDS), α1-acid glycoprotein (AAG), transferrin (TF), ceruloplasmin (CP), neutrophil gelatinase–associated lipocalin (NGAL), and monocyte chemotactic protein 1 (MCP-1). Using nonparametric analyses, levels of urinary biomarkers and established markers of renal function were compared with histologic features seen in LN, i.e., mesangial expansion, capillary proliferation, crescent formation, necrosis, wire loops, fibrosis, tubular atrophy, and epimembranous deposits. The area under the receiver operating characteristic curve (AUC) was calculated to predict LN activity, chronicity, or membranous LN.
Results
There was a differential increase in levels of urinary biomarkers that formed a pattern reflective of specific histologic features seen in active LN. The combination of MCP-1, AAG, and CP levels plus protein:creatinine ratio was excellent in predicting LN activity (AUC 0.85). NGAL together with creatinine clearance plus MCP-1 was an excellent diagnostic test for LN chronicity (AUC 0.83), and the combination of MCP-1, AAG, TF, and creatinine clearance plus C4 was a good diagnostic test for membranous LN (AUC 0.75).
Conclusion
Specific urinary biomarkers are associated with specific tissue changes observed in conjunction with LN activity and chronicity. Especially in combination with select established markers of renal function, urinary biomarkers are well-suited for use in noninvasive measurement of LN activity, LN chronicity, and the presence of membranous LN.