Pre-transplant donor-specific anti-human leukocyte antigen antibodies are associated with high risk of delayed graft function after renal transplantation

Nephrol Dial Transplant. 2016 Apr;31(4):672-8. doi: 10.1093/ndt/gfv391. Epub 2015 Nov 27.

Abstract

Background: 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).

Methods: 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.

Results: 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%).

Conclusions: 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.

Keywords: delayed graft function; dialysis; donor-specific antibody; graft survival; immunology; kidney transplantation.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Delayed Graft Function / immunology*
  • Female
  • Finland / epidemiology
  • Graft Rejection / epidemiology*
  • Graft Rejection / immunology
  • HLA Antigens / blood
  • HLA Antigens / immunology*
  • Humans
  • Incidence
  • Isoantibodies / blood*
  • Isoantibodies / immunology
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Tissue Donors
  • Treatment Outcome

Substances

  • HLA Antigens
  • Isoantibodies