title: Long-term Outcomes of Kidney Transplantation in Patients With High Levels of Preformed DSA: The Necker High-Risk Transplant Program.
abstract: There is an increasing number of anti-HLA sensitized and highly sensitized renal transplant candidates on waiting lists, and the presence of donor-specific alloantibodies (DSAs) at the time of transplantation leads to acute and chronic antibody-mediated rejection (AMR). Acceptable short-term outcomes have been described, notably because of desensitization protocols, but mid- and long-term data are still required.
  
  
  
  Our high immunologic risk program included 95 patients with high peak or day 0 DSA levels (mean fluorescence intensity [MFI] > 3000) with a complement-dependent cytotoxicity-negative crossmatch, who received a posttransplant desensitization protocol starting at day 0 with high-dose intravenous immunoglobulin, plasma exchanges, and eventually rituximab. Their characteristics were compared with a control group including 39 patients with a lower immunologic risk (MFI between 500 and 3000 at day 0) who received the same posttransplant desensitization.
  
  
  
  The median MFI of the immunodominant class I or II DSA in the peak or day 0 serum was 9421 (interquartile range, 4959-12 610). An AMR occurred during the first posttransplant year in 31 patients (32.6%), and at one year, the rate of chronic AMR was 39.5%. The 1-, 3-, 5- and 7-year death-censored allograft survival rates were 98%, 91%, 86%, and 78%, respectively, with concomitant recipient survival rates of 97%, 93%, 85%, and 79%, respectively.
  
  
  
  These results suggest that DSA-sensitized patients with high MFI levels can receive transplantation across the HLA-barrier, with the use of an intensified posttransplant immunosuppressive therapy starting at day 0 combined with close clinical, immunologic, and histologic monitoring.
authors.affiliation: 1 Department of Nephrology-Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Paris, France. 2 INSERM U1151, Paris, France. 3 Paris Translational Research Center for Organ Transplantation, INSERM U970, Paris, France. 4 Department of Immunology and Histocompatibility, Saint-Louis Hospital, Paris, France. 5 Department of Pathology, Necker Hospital, Paris, France. 6 Kidney Transplant Unit, Instituto de Medicina Integral, Recife, Brazil. 7 Department of Urology, Georges Pompidou European Hospital, Paris, France. 8 Department of Anesthesiology, Necker Hospital, Paris, France. 9 Centaure Foundation and Labex Transplantex, Necker Hospital, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Amrouche
authors.forename: Olivier
authors.initials: O
authors.lastname: Aubert
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.forename: Marion
authors.initials: M
authors.lastname: Rabant
authors.forename: Jean-Paul Duong
authors.initials: JD
authors.lastname: Van Huyen
authors.forename: Frank
authors.initials: F
authors.lastname: Martinez
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sberro-Soussan
authors.forename: Anne
authors.initials: A
authors.lastname: Scemla
authors.forename: Claire
authors.initials: C
authors.lastname: Tinel
authors.forename: Renaud
authors.initials: R
authors.lastname: Snanoudj
authors.forename: Julien
authors.initials: J
authors.lastname: Zuber
authors.forename: Ruy
authors.initials: R
authors.lastname: Cavalcanti
authors.forename: Marc-Olivier
authors.initials: MO
authors.lastname: Timsit
authors.forename: Lionel
authors.initials: L
authors.lastname: Lamhaut
authors.forename: Dany
authors.initials: D
authors.lastname: Anglicheau
authors.forename: Alexandre
authors.initials: A
authors.lastname: Loupy
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
mesh_terms: D000328:Adult; D064591:Allografts; D015415:Biomarkers; D046148:Donor Selection; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010297:Paris; D015397:Program Evaluation; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies