title: Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts.
abstract: Kidney allograft rejection can occur in clinically stable patients, but long-term significance is unknown. We determined whether early recognition of subclinical rejection has long-term consequences for kidney allograft survival in an observational prospective cohort study of 1307 consecutive nonselected patients who underwent ABO-compatible, complement-dependent cytotoxicity-negative crossmatch kidney transplantation in Paris (2000-2010). Participants underwent prospective screening biopsies at 1 year post-transplant, with concurrent evaluations of graft complement deposition and circulating anti-HLA antibodies. The main analysis included 1001 patients. Three distinct groups of patients were identified at the 1-year screening: 727 (73%) patients without rejection, 132 (13%) patients with subclinical T cell-mediated rejection (TCMR), and 142 (14%) patients with subclinical antibody-mediated rejection (ABMR). Patients with subclinical ABMR had the poorest graft survival at 8 years post-transplant (56%) compared with subclinical TCMR (88%) and nonrejection (90%) groups (P<0.001). In a multivariate Cox model, subclinical ABMR at 1 year was independently associated with a 3.5-fold increase in graft loss (95% confidence interval, 2.1 to 5.7) along with eGFR and proteinuria (P<0.001). Subclinical ABMR was associated with more rapid progression to transplant glomerulopathy. Of patients with subclinical TCMR at 1 year, only those who further developed de novo donor-specific antibodies and transplant glomerulopathy showed higher risk of graft loss compared with patients without rejection. Our findings suggest that subclinical TCMR and subclinical ABMR have distinct effects on long-term graft loss. Subclinical ABMR detected at the 1-year screening biopsy carries a prognostic value independent of initial donor-specific antibody status, previous immunologic events, current eGFR, and proteinuria.
authors.affiliation: Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France; Paris Descartes University and Hôpital Necker, alexandreloupy@gmail.com.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Loupy
authors.affiliation: Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France; Methodology Unit (EA 3181), CHRU de Besançon, France;
authors.forename: Dewi
authors.initials: D
authors.lastname: Vernerey
authors.affiliation: Paris Descartes University and Hôpital Necker.
authors.forename: Claire
authors.initials: C
authors.lastname: Tinel
authors.affiliation: Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France;
authors.forename: Olivier
authors.initials: O
authors.lastname: Aubert
authors.affiliation: Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France; Department of Pathology, Necker Hospital, Paris, France; and.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Duong van Huyen
authors.affiliation: Department of Pathology, Necker Hospital, Paris, France; and.
authors.forename: Marion
authors.initials: M
authors.lastname: Rabant
authors.affiliation: Department of Pathology, Saint Louis Hospital, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Verine
authors.affiliation: Hôpital Européen Pompidou, and.
authors.forename: Dominique
authors.initials: D
authors.lastname: Nochy
authors.affiliation: Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France;
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Empana
authors.affiliation: Paris Descartes University and Hôpital Necker.
authors.forename: Frank
authors.initials: F
authors.lastname: Martinez
authors.affiliation: Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Denis
authors.initials: D
authors.lastname: Glotz
authors.affiliation: Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France;
authors.forename: Xavier
authors.initials: X
authors.lastname: Jouven
authors.affiliation: Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France; Paris Descartes University and Hôpital Necker.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Carmen
authors.initials: C
authors.lastname: Lefaucheur
mesh_terms: D000328:Adult; D017677:Age Distribution; D064591:Allografts / Q000276:immunology*; D000906:Antibodies / Q000276:immunology; D001707:Biopsy, Needle; D015331:Cohort Studies; D051799:Delayed Graft Function / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D005260:Female; D005602:France; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D066027:Transplant Recipients / Q000706:statistics & numerical data
chemical_list: D000906:Antibodies
keywords: allograft function; allograft loss; renal medicine; translational research; transplant rejection