Differential Impact of Delayed Graft Function in Deceased Donor Renal Transplant Recipients With and Without Donor-specific HLA-antibodies

Transplantation. 2019 Sep;103(9):e273-e280. doi: 10.1097/TP.0000000000002802.

Abstract

Background: Delayed graft function (DGF) and pretransplant donor-specific HLA-antibodies (DSA) are both regarded as risk factors for rejection and lower graft survival. However, the combined impact of DGF and DSA has not been studied in detail.

Methods: We investigated 375 deceased donor kidney transplantations, which had DSA assignment by single-antigen bead technology and which had surveillance biopsies at 3 of 6 months. Median follow-up time was 6.1 years.

Results: DGF occurred in 137 of 375 patients (37%), and DSA were present in 85 of 375 patients (23%). The incidence of DGF was similar in DSA-positive (DSApos)-patients and DSA-negative (DSAneg)-patients (40% versus 36%; P = 0.45). In DSAneg-patients, 5-year graft survival was not different with/without DGF (81% versus 83%; P = 0.48). By contrast, in DSApos-patients, 5-year graft survival was significantly lower with DGF (64% versus 79%; P = 0.01). Moreover, DSApos-patients with DGF had a higher 1-year incidence of subclinical rejection, which were mostly antibody-mediated or mixed rejection phenotypes. Graft loss due to rejection was significantly more frequent in DSApos-patients with DGF (5/34; 15%) compared to DSApos-patients without DGF (2/51; 4%), and DSAneg-patients with/without DGF (3/103; 3% and 4/187; 2%, respectively) (P = 0.005). In a multivariate Cox model, DSA with DGF was an independent predictor for graft (hazard ratio = 2.84 [95% confidence interval, 1.54-5.06]; P = 0.001) and death-censored graft loss (hazard ratio = 4.65 [95% confidence interval, 1.83-11.51]; P = 0.002).

Conclusions: DGF has a much more detrimental impact in DSApos-patients than in DSAneg-patients, which is likely related to a higher incidence of antibody-mediated rejection. If possible, the combined risks of DGF and DSA should be avoided.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Delayed Graft Function / blood
  • Delayed Graft Function / etiology*
  • Delayed Graft Function / immunology
  • Drug Therapy, Combination
  • Female
  • Graft Rejection / blood
  • Graft Rejection / etiology*
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival*
  • HLA Antigens / immunology*
  • Histocompatibility*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Isoantibodies / blood*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use
  • Risk Assessment
  • Risk Factors
  • Tacrolimus / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • HLA Antigens
  • Immunosuppressive Agents
  • Isoantibodies
  • Mycophenolic Acid
  • Tacrolimus