TY - JOUR
T1 - Successful Urine Multiplex Bead Assay to Measure Lupus Nephritis Activity
AU - Cody, Ellen M.
AU - Bennett, Michael R.
AU - Gulati, Gaurav
AU - Ma, Qing
AU - Altaye, Mekibib
AU - Devarajan, Prasad
AU - Brunner, Hermine I.
N1 - Funding Information:
Support was provided by the CCHMC Innovation Fund, Support PORTICO, and Lupus Foundation of America (LFA). HIB is supported by the National Institutes of Arthritis and Musculoskeletal Skin Diseases (NIH) under Award Number P30AR076316 . PD is supported by a grant from the NIDDK (P50 DK096418). We are grateful for the support and samples provided by MedImmune to complete this project. We are also grateful for the support of the NIAMS Cincinnati Rheumatology Core Center Biobank (P30AR070549; Susan Thompson PI) and its assistance of sample storage. This work was completed in partial fulfillment of the Master of Science degree in Clinical and Translational Research in the Division of Epidemiology, University of Cincinnati College of Medicine by EMC.
Funding Information:
HIB, MB, and PD are co-inventors on patents submitted for the use of RAIL biomarkers in lupus nephritis. HIB: Speaking fees for Novartis and Roche (both >$10,000) and GlaxoSmithKline ($10,000 each) from the following industries in the past 3 years: Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, Novartis, and Pfizer. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment to third parties. HIB’s time is supported by supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (grant P30-AR-076316). This work was funded by an Innovation Award from the Cincinnati Children’s research Foundation awarded jointly to PD and HIB. All the other authors declare no competing interests.
Funding Information:
Support was provided by the CCHMC Innovation Fund, Support PORTICO, and Lupus Foundation of America (LFA). HIB is supported by the National Institutes of Arthritis and Musculoskeletal Skin Diseases (NIH) under Award Number P30AR076316. PD is supported by a grant from the NIDDK (P50 DK096418). We are grateful for the support and samples provided by MedImmune to complete this project. We are also grateful for the support of the NIAMS Cincinnati Rheumatology Core Center Biobank (P30AR070549; Susan Thompson PI) and its assistance of sample storage. This work was completed in partial fulfillment of the Master of Science degree in Clinical and Translational Research in the Division of Epidemiology, University of Cincinnati College of Medicine by EMC.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/7
Y1 - 2021/7
N2 - Introduction: Lupus nephritis (LN) confers a poor prognosis, mainly from lack of effective laboratory tests to diagnose and to evaluate therapies. We have previously shown that a set of 6 urinary biomarkers (NGAL, KIM-1, MCP-1, adiponectin, hemopexin, and ceruloplasmin) are highly sensitive and specific to identify adult and pediatric patients with active LN using renal biopsy as reference standard. Using these combinatorial urinary biomarkers, the Renal Activity Score for Lupus (RAIL) score was established, with biomarkers measured by enzyme-linked immunosorbent assay (ELISA). To enhance clinical utility of the biomarkers and RAIL, we tested the performance of RAIL with biomarkers measured by ELISA to that of biomarkers measured by the bead multiplex method, hypothesizing that the multiplex bead method would be comparable. Methods: Spot urine samples (n = 341) of 46 patients aged 20 to 73 years with or without LN were used. Samples were assayed both by ELISA and multiplex using LUMINEX. RAIL scores and biomarker quantities were assessed for agreement with intraassay correlation coefficients and compared using Bland−Altman and regression. Results: Biomarker measurement by LUMINEX was successful for NGAL, KIM-1, MCP-1, and adiponectin, but not for ceruloplasmin and hemopexin. There was good agreement of the RAIL obtained from these 4 biomarkers, irrespective of assay method (intraclass correlation coefficient [ICC] = 0.78, 95% confidence interval [CI] = 0.78−0.82). The RAIL scores from 4 biomarkers further correlated with those when considering all 6 biomarkers (ICC = 0.97, 95% CI = 0.96−0.98). Conclusion: The LUMINEX platform allows for the convenient and simultaneous measurement of 4 RAIL biomarkers. RAIL scores considering only these 4 biomarkers may be sufficient to accurately capture LN activity.
AB - Introduction: Lupus nephritis (LN) confers a poor prognosis, mainly from lack of effective laboratory tests to diagnose and to evaluate therapies. We have previously shown that a set of 6 urinary biomarkers (NGAL, KIM-1, MCP-1, adiponectin, hemopexin, and ceruloplasmin) are highly sensitive and specific to identify adult and pediatric patients with active LN using renal biopsy as reference standard. Using these combinatorial urinary biomarkers, the Renal Activity Score for Lupus (RAIL) score was established, with biomarkers measured by enzyme-linked immunosorbent assay (ELISA). To enhance clinical utility of the biomarkers and RAIL, we tested the performance of RAIL with biomarkers measured by ELISA to that of biomarkers measured by the bead multiplex method, hypothesizing that the multiplex bead method would be comparable. Methods: Spot urine samples (n = 341) of 46 patients aged 20 to 73 years with or without LN were used. Samples were assayed both by ELISA and multiplex using LUMINEX. RAIL scores and biomarker quantities were assessed for agreement with intraassay correlation coefficients and compared using Bland−Altman and regression. Results: Biomarker measurement by LUMINEX was successful for NGAL, KIM-1, MCP-1, and adiponectin, but not for ceruloplasmin and hemopexin. There was good agreement of the RAIL obtained from these 4 biomarkers, irrespective of assay method (intraclass correlation coefficient [ICC] = 0.78, 95% confidence interval [CI] = 0.78−0.82). The RAIL scores from 4 biomarkers further correlated with those when considering all 6 biomarkers (ICC = 0.97, 95% CI = 0.96−0.98). Conclusion: The LUMINEX platform allows for the convenient and simultaneous measurement of 4 RAIL biomarkers. RAIL scores considering only these 4 biomarkers may be sufficient to accurately capture LN activity.
KW - ELISA
KW - RAIL
KW - SLE
KW - lupus
KW - multiplex
KW - nephritis
UR - http://www.scopus.com/inward/record.url?scp=85106367953&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2021.04.016
DO - 10.1016/j.ekir.2021.04.016
M3 - Article
C2 - 34307989
AN - SCOPUS:85106367953
SN - 2468-0249
VL - 6
SP - 1949
EP - 1960
JO - Kidney International Reports
JF - Kidney International Reports
IS - 7
ER -