Urinary CXCL9 and CXCL10 levels correlate with the extent of subclinical tubulitis

Am J Transplant. 2009 Jun;9(6):1347-53. doi: 10.1111/j.1600-6143.2009.02645.x. Epub 2009 May 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / urine
  • Adolescent
  • Adult
  • Aged
  • Alpha-Globulins / urine
  • Biomarkers / urine
  • Chemokine CXCL10 / urine*
  • Chemokine CXCL9 / urine*
  • Female
  • Graft Rejection / urine*
  • Humans
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / pathology
  • Kidney Tubules / pathology
  • Lipocalin-2
  • Lipocalins / urine
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / urine
  • Pyelonephritis / pathology
  • Pyelonephritis / urine*
  • Receptors, CXCR3


  • Acute-Phase Proteins
  • Alpha-Globulins
  • Biomarkers
  • Chemokine CXCL10
  • Chemokine CXCL9
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Receptors, CXCR3
  • alpha-1-microglobulin