title: Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study.
abstract: OBJECTIVE
  To assess the long term outcomes of transplantation using expanded criteria donors (ECD; donors aged ≥ 60 years or aged 50-59 years with vascular comorbidities) and assess the main determinants of its prognosis.
  
  
  METHODS
  Prospective, population based cohort study.
  
  
  METHODS
  Four French referral centres.
  
  
  METHODS
  Consecutive patients who underwent kidney transplantation between January 2004 and January 2011, and were followed up to May 2014. A validation cohort included patients from another four referral centres in France who underwent kidney transplantation between January 2002 and December 2011.
  
  
  METHODS
  Long term kidney allograft survival, based on systematic assessment of donor, recipient, and transplant clinical characteristics; preimplantation biopsy; and circulating levels of donor specific anti-HLA (human leucocyte antigen) antibody (DSA) at baseline.
  
  
  RESULTS
  The study included 6891 patients (2763 in the principal cohort, 4128 in the validation cohort). Of 2763 transplantations performed, 916 (33.2%) used ECD kidneys. Overall, patients receiving ECD transplants had lower allograft survival after seven years than patients receiving transplants from standard criteria donors (SCD; 80% v 88%, P<0.001). Patients receiving ECD transplants who presented with circulating DSA at the time of transplantation had worse allograft survival after seven years than patients receiving ECD kidneys without circulating DSA at transplantation (44% v 85%, P < 0.001). After adjusting for donor, recipient, and transplant characteristics, as well as preimplantation biopsy findings and baseline immunological parameters, the main independent determinants of long term allograft loss were identified as allocation of ECDs (hazard ratio 1.84 (95% confidence interval 1.5 to 2.3); P < 0.001), presence of circulating DSA on the day of transplantation (3.00 (2.3 to 3.9); P < 0.001), and longer cold ischaemia time (> 12 h; 1.53 (1.1 to 2.1); P = 0.011). Recipients of ECD kidneys with circulating DSA showed a 5.6-fold increased risk of graft loss compared with all other transplant therapies (P < 0.001). ECD allograft survival at seven years significantly improved with screening and transplantation in the absence of circulating DSA (P < 0.001) and with shorter (<12 h) cold ischaemia time (P=0.030), respectively. This strategy achieved ECD graft survival comparable to that of patients receiving an SCD transplant overall, translating to a 544.6 allograft life years saved during the nine years of study inclusion time.
  
  
  CONCLUSIONS
  Circulating DSA and cold ischaemia time are the main independent determinants of outcome from ECD transplantation. Allocation policies to avoid DSA and reduction of cold ischaemia time to increase efficacy could promote wider implement of ECD transplantation in the context of organ shortage and improve its prognosis.
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Aubert
authors.affiliation: Department of Nephrology and Organ Transplantation, Rangueil, Toulouse, France INSERM U1043, Purpan, Toulouse Paul Sabatier University, Toulouse DIVAT (Données Informatiques VAlidées en Transplantation Network), France.
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France.
authors.forename: Dewi
authors.initials: D
authors.lastname: Vernerey
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris.
authors.forename: Denis
authors.initials: D
authors.lastname: Viglietti
authors.affiliation: Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris.
authors.forename: Frank
authors.initials: F
authors.lastname: Martinez
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Pathology, Necker Hospital, Paris.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Duong-Van-Huyen
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Renal Physiology, Georges Pompidou European Hospital, Paris.
authors.forename: Dominique
authors.initials: D
authors.lastname: Eladari
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Empana
authors.affiliation: Department of Pathology, Necker Hospital, Paris.
authors.forename: Marion
authors.initials: M
authors.lastname: Rabant
authors.affiliation: Department of Pathology, Saint-Louis Hospital, Paris.
authors.forename: Jerome
authors.initials: J
authors.lastname: Verine
authors.affiliation: Department of Nephrology and Organ Transplantation, Rangueil, Toulouse, France INSERM U1043, Purpan, Toulouse Paul Sabatier University, Toulouse DIVAT (Données Informatiques VAlidées en Transplantation Network), France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.affiliation: Paul Sabatier University, Toulouse Molecular Immunogenetics Laboratory, EA 3034, Faculty of Medicine Purpan, IFR150 (INSERM), Toulouse, France Department of Immunology, Rangueil Hospital, Toulouse.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Congy
authors.affiliation: Paul Sabatier University, Toulouse Department of Pathology, Rangueil, Toulouse.
authors.forename: Céline
authors.initials: C
authors.lastname: Guilbeau-Frugier
authors.affiliation: DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Montpellier, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Mourad
authors.affiliation: DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Montpellier, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Garrigue
authors.affiliation: DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Groupement Hospitalier, Hôpital Edouard Herriot, Lyon, France Centaure Network, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Morelon
authors.affiliation: DIVAT (Données Informatiques VAlidées en Transplantation Network), France Centaure Network, France Department of Nephrology and Kidney Transplantation, Nantes, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
authors.affiliation: DIVAT (Données Informatiques VAlidées en Transplantation Network), France Centaure Network, France Department of Nephrology and Kidney Transplantation, Nancy, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Kessler
authors.affiliation: DIVAT (Données Informatiques VAlidées en Transplantation Network), France Centaure Network, France Department of Nephrology and Kidney Transplantation, Nancy, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Ladrière
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Nephrology and Kidney Transplantation, Foch Hospital, Suresnes, Paris.
authors.forename: Michel
authors.initials: M
authors.lastname: Delahousse
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris.
authors.forename: Denis
authors.initials: D
authors.lastname: Glotz
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris Centaure Network, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Cardiology, Georges Pompidou European Hospital, Paris.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jouven
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris.
authors.forename: Carmen
authors.initials: C
authors.lastname: Lefaucheur
authors.affiliation: Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris alexandreloupy@gmail.com.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Loupy
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D050377:Cold Ischemia; D046148:Donor Selection / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies