Incidence, risk factors, management strategies, and outcomes of antibody-mediated rejection in pediatric kidney transplant recipients-a multicenter analysis of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN)

Pediatr Nephrol. 2025 Feb;40(2):491-503. doi: 10.1007/s00467-024-06487-2. Epub 2024 Sep 16.

Abstract

Background: This study by the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) was designed to determine the incidence, risk factors, current management strategies, and outcomes of antibody-mediated rejection (ABMR) in pediatric kidney transplant recipients (pKTR).

Methods: We performed an international, multicenter, longitudinal cohort study of data reported to the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry. Three hundred thirty-seven pKTR from 21 European centers were analyzed. Clinical outcomes, including kidney dysfunction, rejection, HLA donor-specific antibodies, BK polyomavirus-associated (BKPyV) nephropathy, and allograft loss, were assessed through 5 years post-transplant.

Results: The cumulative incidence of de novo donor-specific class I HLA antibodies (HLA-DSA) post-transplant was 4.5% in year 1, 8.3% in year 3, and 13% in year 5; the corresponding data for de novo class II HLA-DSA were 10%, 22.5%, and 30.6%, respectively. For 5 years post-transplant, the cumulative incidence of acute ABMR was 10% and that of chronic active ABMR was 5.9%. HLA-DR mismatch and de novo HLA-DSA, especially double positivity for class I and class II HLA-DSA, were significant risk factors for ABMR, whereas cytomegalovirus (CMV) IgG negative recipient and CMV IgG negative donor were associated with a lower risk. BKPyV nephropathy was associated with the highest risk of graft dysfunction, followed by ABMR, T-cell mediated rejection, and older donor age.

Conclusions: This study provides an estimate of the incidence of de novo HLA-DSA and ABMR in pKTR and highlights the importance of BKPyV nephropathy as a strong risk factor for allograft dysfunction.

Keywords: DnDSA development; Antibody-mediated rejection; BKPyV nephropathy; Graft outcome; Pediatric kidney transplantation; Risk factors.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Europe / epidemiology
  • Female
  • Graft Rejection* / epidemiology
  • Graft Rejection* / immunology
  • Graft Survival / immunology
  • HLA Antigens / immunology
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Infant
  • Isoantibodies / blood
  • Isoantibodies / immunology
  • Kidney Transplantation* / adverse effects
  • Longitudinal Studies
  • Male
  • Polyomavirus Infections / epidemiology
  • Polyomavirus Infections / immunology
  • Registries / statistics & numerical data
  • Risk Factors
  • Treatment Outcome

Substances

  • Isoantibodies
  • HLA Antigens
  • Immunosuppressive Agents