Donor Specificity but Not Broadness of Sensitization Is Associated With Antibody-Mediated Rejection and Graft Loss in Renal Allograft Recipients

Am J Transplant. 2017 Aug;17(8):2092-2102. doi: 10.1111/ajt.14247. Epub 2017 Mar 27.

Abstract

Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the "calculated population-reactive antibodies" (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor-specific HLA antibodies (DSA). Five hundred twenty-seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1-50% (n = 129), cPRA 51-100% (n = 43), and DSA (n = 105). Patients without DSA were considered as normal risk and received standard immunosuppression without T cell-depleting induction. Patients with DSA received an enhanced induction therapy and maintenance immunosuppression. Surveillance biopsies were performed at 3 and 6 months. Median follow-up was 5.7 years. Among the three cPRA groups, there were no differences regarding the 1-year incidence of ABMR (p = 0.16) and TCMR (p = 0.75). The 5-year allograft survival rates were similar and around 87% (p = 0.28). The estimated glomerular filtration rate at last follow-up was 50-53 mL/min (p = 0.45). On multivariable Cox proportional hazard analysis, the strongest independent predictor for ABMR and (death-censored) graft survival was pretransplantation DSA. cPRA were not predictive for ABMR, TCMR, or (death-censored) graft survival. We conclude that with current DSA assignment, the broadness of sensitization measured by cPRA does not imply an immunological risk.

Keywords: clinical research/practice; histocompatibility; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; major histocompatibility complex (MHC); panel reactive antibody (PRA); risk assessment/risk stratification.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / epidemiology
  • Graft Rejection / immunology*
  • Graft Rejection / mortality
  • Graft Survival / immunology*
  • HLA Antigens / immunology*
  • Humans
  • Incidence
  • Isoantibodies / immunology*
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Tissue Donors

Substances

  • HLA Antigens
  • Isoantibodies