title: Urinary Soluble CD163 in Active Renal Vasculitis.
abstract: A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV.
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Vincent P
authors.initials: VP
authors.lastname: O'Reilly
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Limy
authors.initials: L
authors.lastname: Wong
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Claire
authors.initials: C
authors.lastname: Kennedy
authors.affiliation: Department of Immunology, Trinity College Dublin, Dublin, Ireland;
authors.forename: Louise A
authors.initials: LA
authors.lastname: Elliot
authors.affiliation: HRB Clinical Research Facility, St James's Hospital, Dublin, Ireland;
authors.forename: Shane
authors.initials: S
authors.lastname: O'Meachair
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Alice Marie
authors.initials: AM
authors.lastname: Coughlan
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Eoin C
authors.initials: EC
authors.lastname: O'Brien
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Ryan
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Diego
authors.initials: D
authors.lastname: Sandoval
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Emma
authors.initials: E
authors.lastname: Connolly
authors.affiliation: Department of Nephrology, and.
authors.forename: Gerjan J
authors.initials: GJ
authors.lastname: Dekkema
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Lau
authors.affiliation: Department of Medical Biology and Pathology, University of Groningen, University Medical Center Groningen, The Netherlands;
authors.forename: Wayel H
authors.initials: WH
authors.lastname: Abdulahad
authors.affiliation: Department of Nephrology, and.
authors.forename: Jan-Stephan F
authors.initials: JS
authors.lastname: Sanders
authors.affiliation: Department of Medical Biology and Pathology, University of Groningen, University Medical Center Groningen, The Netherlands;
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.affiliation: Department of Renal Histopathology, Beaumont Hospital, Dublin, Ireland;
authors.forename: Colm
authors.initials: C
authors.lastname: Buckley
authors.affiliation: Labmed Directorate, St James's Hospital, Dublin, Ireland; Department of Histopathology, Trinity College Dublin, Ireland;
authors.forename: Cathal
authors.initials: C
authors.lastname: O'Brien
authors.affiliation: Labmed Directorate, St James's Hospital, Dublin, Ireland; Department of Histopathology, Trinity College Dublin, Ireland;
authors.forename: Stephen
authors.initials: S
authors.lastname: Finn
authors.affiliation: Nephrological Center, Medical Clinic and Policlinic IV, University of Munich, Munich, Germany;
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.affiliation: Nephrological Center, Medical Clinic and Policlinic IV, University of Munich, Munich, Germany;
authors.forename: Maja T
authors.initials: MT
authors.lastname: Lindemeyer
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Fionnuala B
authors.initials: FB
authors.lastname: Hickey
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Hara
authors.affiliation: Department of Immunology, Trinity College Dublin, Dublin, Ireland;
authors.forename: Conleth
authors.initials: C
authors.lastname: Feighery
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Moran
authors.affiliation: Trinity Health Kidney Centre.
authors.forename: George
authors.initials: G
authors.lastname: Mellotte
authors.affiliation: Department of Renal Medicine, Cork University Hospital, Cork, Ireland; and.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clarkson
authors.affiliation: Department of Renal Histopathology, Beaumont Hospital, Dublin, Ireland;
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Dorman
authors.affiliation: School of Medicine, University College Dublin, Dublin, Ireland.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Murray
authors.affiliation: Trinity Health Kidney Centre, mlittle@tcd.ie.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Little
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000652:urine*; D015214:Antigens, Differentiation, Myelomonocytic / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D005260:Female; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D007674:Kidney Diseases / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface; D014657:Vasculitis / Q000652:urine*; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface
keywords: ANCA; glomerulonephritis; immunology; nephrology; renal injury; vasculitis