title: Validation of urinary CXCL10 as a marker of borderline, subclinical, and clinical tubulitis.
abstract: BACKGROUND
  Renal allograft injury secondary to subclinical and clinical tubulitis remains an important cause of allograft fibrosis and loss despite modern immunosuppression. The goal of this study was to validate the previously reported use of urinary CXCL10 (interferon-γ-induced protein of 10 kDa) as a noninvasive marker of tubulitis in an independent clinical cohort.
  
  
  METHODS
  Urine samples (n=102) from 91 patients with protocol or indication biopsies were assayed for urinary CXCL10 using ELISA. The groups analyzed were as follows: normal histology (n=22); interstitial fibrosis and tubular atrophy (IFTA) (n=20); IFTA and borderline tubulitis (n=13); borderline (n=13), subclinical (n=17); and clinical tubulitis (n=17) without IFTA.
  
  
  RESULTS
  The ratio of urinary CXCL10 to creatinine (CXCL10: Cr) was found to distinguish borderline, subclinical and clinical tubulitis from normal histology, and IFTA. The area under the curve receiver operating characteristic curve to distinguish normal versus borderline and subclinical tubulitis was 0.845 (OR 1.407, P=0.0184); normal versus borderline, subclinical and clinical tubulitis was 0.835 (OR 1.400, P=0.0127). CXCL10: Cr demonstrated a sensitivity of 73.3% and specificity of 72.7% for normal versus borderline and subclinical tubulitis at a cut-off of 1.97 ng CXCL10/mmol Cr.
  
  
  CONCLUSIONS
  This study validates urinary CXCL10 as a noninvasive, sensitive, and specific marker for tubulitis in an independent cohort. The straightforward urine processing is accessible to clinical laboratories. We propose that CXCL10 may be useful as a supplementary noninvasive screening test for tubulitis in renal transplant patients, with a level more than 1.97 ng CXCL10/mmol Cr being a threshold to consider biopsy.
authors.affiliation: Section of Nephrology, Health Sciences Centre, University of Manitoba, Winnipeg, MB, Canada. jho@hsc.mb.ca
authors.forename: Julie
authors.initials: J
authors.lastname: Ho
authors.forename: David N
authors.initials: DN
authors.lastname: Rush
authors.forename: Martin
authors.initials: M
authors.lastname: Karpinski
authors.forename: Leroy
authors.initials: L
authors.lastname: Storsley
authors.forename: Ian W
authors.initials: IW
authors.lastname: Gibson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bestland
authors.forename: Ang
authors.initials: A
authors.lastname: Gao
authors.forename: William
authors.initials: W
authors.lastname: Stefura
authors.forename: Kent T
authors.initials: KT
authors.lastname: HayGlass
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nickerson
mesh_terms: D000328:Adult; D001284:Atrophy; D015415:Biomarkers / Q000652:urine; D054357:Chemokine CXCL10 / Q000502:physiology / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000175:diagnosis* / Q000652:urine
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10