title: Early Low Urinary CXCL9 and CXCL10 Might Predict Immunological Quiescence in Clinically and Histologically Stable Kidney Recipients.
abstract: We monitored the urinary C-X-C motif chemokine (CXCL)9 and CXCL10 levels in 1722 urine samples from 300 consecutive kidney recipients collected during the first posttransplantation year and assessed their predictive value for subsequent acute rejection (AR). The trajectories of urinary CXCL10 showed an early increase at 1 month (p = 0.0005) and 3 months (p = 0.0009) in patients who subsequently developed AR. At 1 year, the AR-free allograft survival rates were 90% and 54% in patients with CXCL10:creatinine (CXCL10:Cr) levels <2.79 ng/mmoL and >2.79 ng/mmoL at 1 month, respectively (p < 0.0001), and 88% and 56% in patients with CXCL10:Cr levels <5.32 ng/mmoL and >5.32 ng/mmoL at 3 months (p < 0.0001), respectively. CXCL9:Cr levels also associate, albeit less robustly, with AR-free allograft survival. Early CXCL10:Cr levels predicted clinical and subclinical rejection and both T cell- and antibody-mediated rejection. In 222 stable patients, CXCL10:Cr at 3 months predicted AR independent of concomitant protocol biopsy results (p = 0.009). Although its positive predictive value was low, a high negative predictive value suggests that early CXCL10:Cr might predict immunological quiescence on a triple-drug calcineurin inhibitor-based immunosuppressive regimen in the first posttransplantation year, even in clinically and histologically stable patients. The clinical utility of this test will need to be addressed by dedicated prospective clinical trials.
authors.affiliation: Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France.|Paris Descartes, Sorbonne Paris Cité University, Paris, France.|Pathology Department, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Rabant
authors.affiliation: Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Amrouche
authors.affiliation: Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Morin
authors.affiliation: Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Bonifay
authors.affiliation: Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.|Centaure Foundation and Labex Transplantex, Necker Hospital, Paris, France.
authors.forename: X
authors.initials: X
authors.lastname: Lebreton
authors.affiliation: Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Aouni
authors.affiliation: Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Benon
authors.affiliation: Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Sauvaget
authors.affiliation: Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Le Vaillant
authors.affiliation: Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Aulagnon
authors.affiliation: Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Sberro
authors.affiliation: Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Snanoudj
authors.affiliation: Paris Descartes, Sorbonne Paris Cité University, Paris, France.|Department of Urology, Georges Pompidou European Hospital-Necker, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Mejean
authors.affiliation: Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France.|Paris Descartes, Sorbonne Paris Cité University, Paris, France.|Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.|Centaure Foundation and Labex Transplantex, Necker Hospital, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Terzi
authors.affiliation: Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France.|Paris Descartes, Sorbonne Paris Cité University, Paris, France.|Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.|Centaure Foundation and Labex Transplantex, Necker Hospital, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Anglicheau
mesh_terms: D015415:Biomarkers / Q000652:urine*; D054357:Chemokine CXCL10 / Q000652:urine*; D054370:Chemokine CXCL9 / Q000652:urine*; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9