Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for kidney transplant injury

Am J Transplant. 2013 Oct;13(10):2634-44. doi: 10.1111/ajt.12426. Epub 2013 Aug 22.


Noninvasive biomarkers are needed to assess immune risk and ultimately guide therapeutic decision-making following kidney transplantation. A requisite step toward these goals is validation of markers that diagnose and/or predict relevant transplant endpoints. The Clinical Trials in Organ Transplantation-01 protocol is a multicenter observational study of biomarkers in 280 adult and pediatric first kidney transplant recipients. We compared and validated urinary mRNAs and proteins as biomarkers to diagnose biopsy-proven acute rejection (AR) and stratify patients into groups based on risk for developing AR or progressive renal dysfunction. Among markers tested for diagnosing AR, urinary CXCL9 mRNA (odds ratio [OR] 2.77, positive predictive value [PPV] 61.5%, negative predictive value [NPV] 83%) and CXCL9 protein (OR 3.40, PPV 67.6%, NPV 92%) were the most robust. Low urinary CXCL9 protein in 6-month posttransplant urines obtained from stable allograft recipients classified individuals least likely to develop future AR or a decrement in estimated glomerular filtration rate between 6 and 24 months (92.5-99.3% NPV). Our results support using urinary CXCL9 for clinical decision-making following kidney transplantation. In the context of acute dysfunction, low values can rule out infectious/immunological causes of injury. Absent urinary CXCL9 at 6 months posttransplant defines a subgroup at low risk for incipient immune injury.

Keywords: Acute rejection; biomarker; chemokines; kidney allograft; kidney graft function.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Acute Kidney Injury / surgery
  • Acute Kidney Injury / urine*
  • Adult
  • Biomarkers / blood
  • Biomarkers / urine*
  • Chemokine CXCL9 / blood
  • Chemokine CXCL9 / urine*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / etiology
  • Graft Rejection / urine*
  • Humans
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Prognosis
  • Prospective Studies
  • Risk Factors


  • Biomarkers
  • CXCL9 protein, human
  • Chemokine CXCL9