title: Urinary CXCL9 and CXCL10 levels correlate with the extent of subclinical tubulitis.
abstract: Subclinical tubulitis has been associated with the later development of interstitial fibrosis and tubular atrophy (IF/TA), leading to diminished allograft survival. The aim of this study was to investigate how concentrations of urinary CXC-receptor 3 (CXCR3) chemokines (i.e. CXCL4/9/10/11) and CCL2 relate to the extent of subclinical tubulitis. Using ELISA, urinary CXCR3 chemokines, CCL2 and tubular injury markers (i.e. urinary NGAL and alpha1-microglobulin [alpha1 m]) were measured in patients with stable estimated GFR >or=40 mL/min exhibiting normal tubular histology (n = 24), subclinical borderline tubulitis (n = 18) or subclinical tubulitis Ia/Ib (n = 22), as well as in patients with clinical tubulitis Ia/Ib (n = 17) or IF/TA (n = 10). CXCL9 and CXCL10 were significantly higher in subclinical tubulitis Ia/Ib than in subclinical borderline tubulitis (p <or= 0.03) and normal tubular histology (p <or= 0.0002). By contrast, NGAL, alpha1-m, CXCL4, CXCL11 and CCL2 were not or only marginally distinctive across these patient groups. All urinary chemokines and tubular injury markers were higher in clinical tubulitis Ia/Ib than in normal tubular histology (p <or= 0.002), but only tubular injury markers were elevated in IF/TA. These results demonstrate a correlation of urinary CXCL9 and CXCL10 levels with the extent of subclinical tubulitis suggesting potential as noninvasive screening biomarkers.
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland. schaubs@uhbs.ch
authors.forename: S
authors.initials: S
authors.lastname: Schaub
authors.forename: P
authors.initials: P
authors.lastname: Nickerson
authors.forename: D
authors.initials: D
authors.lastname: Rush
authors.forename: M
authors.initials: M
authors.lastname: Mayr
authors.forename: C
authors.initials: C
authors.lastname: Hess
authors.forename: M
authors.initials: M
authors.lastname: Golian
authors.forename: W
authors.initials: W
authors.lastname: Stefura
authors.forename: K
authors.initials: K
authors.lastname: Hayglass
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000510:Alpha-Globulins / Q000652:urine; D015415:Biomarkers / Q000652:urine; D054357:Chemokine CXCL10 / Q000652:urine*; D054370:Chemokine CXCL9 / Q000652:urine*; D005260:Female; D006084:Graft Rejection / Q000652:urine*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine; D011704:Pyelonephritis / Q000473:pathology / Q000652:urine*; D054367:Receptors, CXCR3
chemical_list: D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D015415:Biomarkers; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D054367:Receptors, CXCR3; C016001:alpha-1-microglobulin