title: Elevated urinary CCL2: Cr at 6 months is associated with renal allograft interstitial fibrosis and inflammation at 24 months.
abstract: BACKGROUND
  We have demonstrated that 6-month urinary CCL2: Cr is a predictor of interstitial fibrosis and tubular atrophy (IFTA) on 24-month biopsy and death-censored graft loss. However, IFTA is no longer considered prognostically significant, whereas patients with graft loss frequently have interstitial fibrosis and inflammation (IF+i=ci>0+i>0). As early CCL2: Cr predicts late graft loss, the goal of this study was to determine if 6-month urinary CCL2: Cr was a predictor of IF+i at 24 months.
  
  
  METHODS
  Urinary CCL2 at 6 months was measured with ELISA and correlated with IF+i on 24-month surveillance biopsies from a prospective, multicenter adult renal transplant cohort (n=111).
  
  
  RESULTS
  Six-month urinary CCL2: Cr was significantly higher in IF+i and transplant glomerulopathy patients compared with normal histology at 24 months. By multivariate analysis, 6-month urinary CCL2: Cr was independently correlated with IF+i at 24 months (OR 2.78, 95% CI 1.38-6.12, AUC 0.695, P=0.003). Six-month urinary CCL2: Cr was also an independent correlate of 6-month IF+i (OR 1.99, 95% CI 1.03-4.18, AUC 0.63, P=0.04). Six-month urinary CCL2: Cr distinguished noninflamed renal tissue (normal, fibrosis) from IF+i with a sensitivity/specificity of 0.71/0.62 at a cutoff of 15 ng CCL2/mmol Cr (AUC 0.695, P=0.003, n=91).
  
  
  CONCLUSIONS
  Urinary CCL2: Cr may be useful for the noninvasive identification of patients with or at risk for IF+i. These patients may benefit from avoidance of drug minimization/withdrawal protocols and more intensive post-transplant surveillance. Furthermore, urinary CCL2: Cr may also identify individuals who may benefit from novel interventional trials targeting IF+i.
authors.affiliation: 1 Section of Nephrology, University of Manitoba, Winnipeg, Manitoba, Canada. 2 Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Manitoba, Canada. 3 Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada. 4 Department of Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada. 5 Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada. 6 Address correspondence to: Julie Ho, M.D., F.R.C.P.C., Sections of Nephrology and Biomedical Proteomics, Health Sciences Centre, GE421C, 820 Sherbrook Street, Winnipeg, MB R3A 1R9.
authors.forename: Julie
authors.initials: J
authors.lastname: Ho
authors.forename: Chris
authors.initials: C
authors.lastname: Wiebe
authors.forename: Ian W
authors.initials: IW
authors.lastname: Gibson
authors.forename: Sabine
authors.initials: S
authors.lastname: Hombach-Klonisch
authors.forename: Ang
authors.initials: A
authors.lastname: Gao
authors.forename: Claudio
authors.initials: C
authors.lastname: Rigatto
authors.forename: Martin
authors.initials: M
authors.lastname: Karpinski
authors.forename: Leroy
authors.initials: L
authors.lastname: Storsley
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nickerson
authors.forename: David N
authors.initials: DN
authors.lastname: Rush
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D002170:Canada; D018932:Chemokine CCL2 / Q000652:urine*; D016009:Chi-Square Distribution; D002908:Chronic Disease; D003404:Creatinine / Q000652:urine*; D005260:Female; D005355:Fibrosis; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009395:Nephritis, Interstitial / Q000276:immunology / Q000473:pathology / Q000652:urine*; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014481:United States; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003404:Creatinine