title: Pre-transplant donor-specific anti-human leukocyte antigen antibodies are associated with high risk of delayed graft function after renal transplantation.
abstract: Sensitive screening methods have revealed that many patients have donor-specific human leucocyte antigen antibodies (DSAs) prior to transplantation, regardless of negative crossmatch results. The clinical significance of pre-transplant (pre-Tx) DSAs for early graft function has remained unclear. Our aim was to examine the association of DSAs with delayed graft function (DGF).
  
  
  
  Pre-Tx sera of 771 patients who received kidney transplants in our single-centre study were retrospectively screened. All transplantations were performed after negative complement-dependent cytotoxicity (CDC) crossmatch.
  
  
  
  DSAs were detected in 13% of the patients. The overall DGF rate in our study was 29%. Patients with DSAs had a higher incidence of DGF when compared with non-sensitized patients (48 and 26%, respectively; P < 0.0001). Third-party antibodies had no effect for DGF incidence (28%; P = 0.6098). The relative risk (RR) of DGF for patients with DSAs in the multivariate analysis was 2.039 (95% CI 1.246-3.335; P = 0.0046). Analyses of the cumulative mean fluorescent intensity (MFI) value of the DSAs revealed a rate of DGF more than two times higher in patients with a cumulative value of 3000-5000 MFI compared with a cumulative value of 1000-3000 (65 versus 31%; P = 0.0351). DSAs against any loci showed an elevated DGF incidence of 44-69% when compared with patients without DSA (27%).
  
  
  
  The risk of DGF is twice as high in patients having pre-formed DSAs. Pre-Tx DSAs is a modifiable risk factor that can be obviated with careful organ allocation relying on careful pre-Tx analysis of non-accepted mismatches determined with sensitive solid phase methods.
authors.affiliation: Clinical Laboratory, Finnish Red Cross Blood Service, Kivihaantie 7, 00310 Helsinki, Finland.
authors.forename: Juha P
authors.initials: JP
authors.lastname: Peräsaari
authors.affiliation: Department of Transplantation and Liver Surgery, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Lauri E
authors.initials: LE
authors.lastname: Kyllönen
authors.affiliation: Department of Transplantation and Liver Surgery, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Kaija T
authors.initials: KT
authors.lastname: Salmela
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Jussi M
authors.initials: JM
authors.lastname: Merenmies
mesh_terms: D000328:Adult; D051799:Delayed Graft Function / Q000276:immunology*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D015994:Incidence; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: delayed graft function; dialysis; donor-specific antibody; graft survival; immunology; kidney transplantation