Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis.


Journal

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402

Informations de publication

Date de publication:
01 02 2020
Historique:
received: 12 04 2018
accepted: 18 08 2018
pubmed: 1 11 2018
medline: 12 9 2020
entrez: 1 11 2018
Statut: ppublish

Résumé

Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples that included new diagnoses with highly active renal disease. This study focused on the use of usCD163 in the detection of the more clinically relevant state of mild renal flare and compared results of usCD163 testing directly to testing of urinary monocyte chemoattractant protein-1 (uMCP-1). Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV, n = 88) were identified within a serially sampled, longitudinal and multicentre cohort. Creatinine-normalized usCD163 and uMCP-1 levels were measured by enzyme-linked immunosorbent assay and, both alone and in combination, were compared between times of active renal AAV and during remission and/or active non-renal AAV. Samples from 320 study visits included times of active renal vasculitis (n = 39), remission (n = 233) and active extrarenal vasculitis (n = 48). Median creatinine levels were 0.9 mg/dL [interquartile range (IQR) 0.8-1.2] in remission and 1.4 mg/dL (IQR 1.0-1.8) during renal flare. usCD163 levels were higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 162 ng/mmol (IQR 79-337), 44 (17-104) and 38 (7-76), respectively (P < 0.001). uMCP-1 levels were also higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 10.6 pg/mmol (IQR 4.6-23.5), 4.1 (2.5-8.4) and 4.1 (1.9-6.8), respectively (P < 0.001). The proposed diagnostic cut-points for usCD163 and uMCP-1 were 72.9 ng/mmol and 10.0 pg/mmol, respectively. usCD163 and uMCP-1 levels were marginally correlated (r2 = 0.11, P < 0.001). Combining novel and existing biomarkers using recursive tree partitioning indicated that elevated usCD163 plus either elevated uMCP-1 or new/worse proteinuria improved the positive likelihood ratio (PLR) of active renal vasculitis to 19.2. A combination of usCD163 and uMCP-1 measurements appears to be useful in identifying the diagnosis of subtle renal vasculitis flare.

Sections du résumé

BACKGROUND
Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples that included new diagnoses with highly active renal disease. This study focused on the use of usCD163 in the detection of the more clinically relevant state of mild renal flare and compared results of usCD163 testing directly to testing of urinary monocyte chemoattractant protein-1 (uMCP-1).
METHODS
Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV, n = 88) were identified within a serially sampled, longitudinal and multicentre cohort. Creatinine-normalized usCD163 and uMCP-1 levels were measured by enzyme-linked immunosorbent assay and, both alone and in combination, were compared between times of active renal AAV and during remission and/or active non-renal AAV.
RESULTS
Samples from 320 study visits included times of active renal vasculitis (n = 39), remission (n = 233) and active extrarenal vasculitis (n = 48). Median creatinine levels were 0.9 mg/dL [interquartile range (IQR) 0.8-1.2] in remission and 1.4 mg/dL (IQR 1.0-1.8) during renal flare. usCD163 levels were higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 162 ng/mmol (IQR 79-337), 44 (17-104) and 38 (7-76), respectively (P < 0.001). uMCP-1 levels were also higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 10.6 pg/mmol (IQR 4.6-23.5), 4.1 (2.5-8.4) and 4.1 (1.9-6.8), respectively (P < 0.001). The proposed diagnostic cut-points for usCD163 and uMCP-1 were 72.9 ng/mmol and 10.0 pg/mmol, respectively. usCD163 and uMCP-1 levels were marginally correlated (r2 = 0.11, P < 0.001). Combining novel and existing biomarkers using recursive tree partitioning indicated that elevated usCD163 plus either elevated uMCP-1 or new/worse proteinuria improved the positive likelihood ratio (PLR) of active renal vasculitis to 19.2.
CONCLUSION
A combination of usCD163 and uMCP-1 measurements appears to be useful in identifying the diagnosis of subtle renal vasculitis flare.

Identifiants

pubmed: 30380100
pii: 5151289
doi: 10.1093/ndt/gfy300
pmc: PMC8205505
doi:

Substances chimiques

Antibodies, Antineutrophil Cytoplasmic 0
Antigens, CD 0
Antigens, Differentiation, Myelomonocytic 0
Biomarkers 0
CCL2 protein, human 0
CD163 antigen 0
Chemokine CCL2 0
Receptors, Cell Surface 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

283-291

Subventions

Organisme : NCATS NIH HHS
ID : U2C TR002818
Pays : United States
Organisme : NCRR NIH HHS
ID : U54 RR019497
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Références

J Am Soc Nephrol. 2000 Nov;11(11):2036-2043
pubmed: 11053479
Ann Rheum Dis. 2010 Jun;69(6):1036-43
pubmed: 19574233
Ann Intern Med. 1999 Mar 16;130(6):461-70
pubmed: 10075613
J Leukoc Biol. 2010 Dec;88(6):1201-5
pubmed: 20807704
Nephrol Dial Transplant. 2016 Dec;31(12):1970-1972
pubmed: 27358273
Ann Rheum Dis. 2009 Dec;68(12):1827-32
pubmed: 19054820
Nephrol Dial Transplant. 2016 Dec;31(12):2023-2033
pubmed: 27242373
Scand J Clin Lab Invest. 2012 Feb;72(1):1-13
pubmed: 22060747
Am J Nephrol. 2016;43(2):112-9
pubmed: 27003681
Clin J Am Soc Nephrol. 2015 Jan 7;10(1):54-62
pubmed: 25516918
J Am Soc Nephrol. 2016 Sep;27(9):2906-16
pubmed: 26940094
Cancer. 1950 Jan;3(1):32-5
pubmed: 15405679
J Rheumatol. 2013 May;40(5):674-83
pubmed: 23547217
Nephrol Dial Transplant. 2004 Nov;19(11):2761-8
pubmed: 15353578
Am J Pathol. 2005 Nov;167(5):1207-19
pubmed: 16251406

Auteurs

Sarah M Moran (SM)

Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland.

Paul A Monach (PA)

Section of Rheumatology, Boston University School of Medicine, Boston, MA, USA.
Rheumatology Section, VA Boston Healthcare System, Boston, MA, USA.

Lina Zgaga (L)

Department of Public Health and General Practice, Trinity College Dublin, Dublin, Ireland.

David Cuthbertson (D)

Department of Biostatistics and Informatics, Department of Pediatrics, University of South Florida, Tampa, FL, USA.

Simon Carette (S)

Division of Rheumatology, Mount Sinai Hospital, Toronto, ON, Canada.

Nader A Khalidi (NA)

Division of Rheumatology, St. Joseph's Healthcare, McMaster University, Hamilton, ON, Canada.

Curry L Koening (CL)

Division of Rheumatology, University of Utah, Salt Lake City, UT, USA.

Carol A Langford (CA)

Division of Rheumatology, Cleveland Clinic, Cleveland, OH, USA.

Carol A McAlear (CA)

Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, USA.

Larry Moreland (L)

Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA.

Christian Pagnoux (C)

Division of Rheumatology, Mount Sinai Hospital, Toronto, ON, Canada.

Philip Seo (P)

Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USA.

Ulrich Specks (U)

Division of Pulmonology, Mayo Clinic College of Medicine, Rochester, MN, USA.

Antoine Sreih (A)

Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, USA.

Jason Wyse (J)

Discipline of Statistics, School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland.

Steven R Ytterberg (SR)

Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN, USA.

Peter A Merkel (PA)

Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA.

Mark A Little (MA)

Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland.
Irish Centre for Vascular Biology, Trinity College Dublin, Dublin, Ireland.

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Classifications MeSH