title: Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for kidney transplant injury.
abstract: 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.
authors: University Hospitals Case Medical Center, Cleveland, OH.
authors: D E
authors: DE
authors: Hricik
authors: P
authors: P
authors: Nickerson
authors: R N
authors: RN
authors: Formica
authors: E D
authors: ED
authors: Poggio
authors: D
authors: D
authors: Rush
authors: K A
authors: KA
authors: Newell
authors: J
authors: J
authors: Goebel
authors: I W
authors: IW
authors: Gibson
authors: R L
authors: RL
authors: Fairchild
authors: M
authors: M
authors: Riggs
authors: K
authors: K
authors: Spain
authors: D
authors: D
authors: Ikle
authors: N D
authors: ND
authors: Bridges
authors: P S
authors: PS
authors: Heeger
mesh_terms: D058186:Acute Kidney Injury / Q000601:surgery / Q000652:urine*; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine*; D054370:Chemokine CXCL9 / Q000097:blood / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000652:urine*; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9
keywords: Acute rejection; biomarker; chemokines; kidney allograft; kidney graft function
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