title: Increased urinary CCL2: Cr ratio at 6 months is associated with late renal allograft loss.
abstract: BACKGROUND
  Early noninvasive markers that identify patients at risk of renal allograft loss may stratify patients for more intensive monitoring or therapy. CCL2 is a CCR2 receptor chemokine that is a chemoattractant protein for monocytes/macrophages, T cells, and natural killer cells. We have previously demonstrated in a multicenter cohort that urinary CCL2 at 6 months is an independent predictor for the development of IFTA at 24 months. The goal of this study was to determine if early urinary CCL2 is a predictor of graft loss in an independent patient cohort.
  
  
  METHODS
  A prospective, observational cohort study was conducted in the Transplant Manitoba Adult Kidney Program (n=231 patients) from 1997 to 2008. Six-month urinary CCL2 was measured by ELISA, corrected for urinary creatinine, and correlated with long-term graft outcomes.
  
  
  RESULTS
  Urine CCL2: Cr at 6 months was significantly associated with death-censored graft loss (HR, 2.42; 95% CI, 1.54-3.82, P<0.0001). On multivariate analysis, urinary CCL2: Cr at 6 months remained an independent predictor of death-censored graft loss (HR, 2.20; 95% CI, 1.18-4.10, P=0.01) after adjustment for pretransplant/de novo donor-specific antibody and delayed graft function. An early posttransplant (≤6 months) multivariate model of CCL2, recipient age, and delayed graft function yielded an AUC 0.87 for prediction of death-censored graft loss. A cutoff value of urinary CCL2: Cr 34.8 ng/mmol yielded a strong positive predictive value of 0.96.
  
  
  CONCLUSIONS
  This study confirms in an independent prospective cohort that early urinary CCL2 at 6 months is a noninvasive, independent predictor for late renal allograft loss.
authors.affiliation: Section of Nephrology, University of Manitoba, Winnipeg, Manitoba, Canada. jho@hsc.mb.ca
authors.forename: Julie
authors.initials: J
authors.lastname: Ho
authors.forename: Chris
authors.initials: C
authors.lastname: Wiebe
authors.forename: David N
authors.initials: DN
authors.lastname: Rush
authors.forename: Claudio
authors.initials: C
authors.lastname: Rigatto
authors.forename: Leroy
authors.initials: L
authors.lastname: Storsley
authors.forename: Martin
authors.initials: M
authors.lastname: Karpinski
authors.forename: Ang
authors.initials: A
authors.lastname: Gao
authors.forename: Ian W
authors.initials: IW
authors.lastname: Gibson
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nickerson
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000652:urine; D018932:Chemokine CCL2 / Q000652:urine*; D003404:Creatinine / Q000652:urine; D051799:Delayed Graft Function / Q000209:etiology / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006085:Graft Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008350:Manitoba; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003404:Creatinine