Risk of cellular or antibody-mediated rejection in pediatric kidney transplant recipients with BK polyomavirus replication-an international CERTAIN registry study

Pediatr Nephrol. 2025 Mar;40(3):835-848. doi: 10.1007/s00467-024-06501-7. Epub 2024 Oct 11.

Abstract

Background: In kidney transplant recipients (KTR), BK polyomavirus-associated nephropathy (BKPyVAN) is a major cause of graft loss. To facilitate the clearance of BKPyV-DNAemia, reduction of immunosuppression is currently the treatment of choice but may increase the risk of graft rejection.

Methods: This international CERTAIN study was designed to determine the risk of alloimmune response and graft dysfunction associated with immunosuppression reduction for BKPyV treatment in 195 pediatric KTR.

Results: BKPyV-DNAemia was associated with a more than twofold increased risk of late T cell-mediated rejection (TCMR) (HR 2.22, p = 0.024), of de novo donor-specific HLA antibodies (dnDSA) and/or antibody-mediated rejection (ABMR) (HR 2.64, p = 0.002), and of graft function deterioration (HR 2.73, p = 0.001). Additional independent risk factors for dnDSA/ABMR development were a higher HLA mismatch (HR 2.72, p = 0.006) and re-transplantation (HR 6.40, p = 0.000). Other independent predictors of graft function deterioration were TCMR (HR 3.98, p = 0.003), higher donor age (HR 1.03, p = 0.020), and re-transplantation (HR 3.56, p = 0.013).

Conclusions: These data indicate that reduction of immunosuppression for BKPyV-DNAemia management is associated with increased alloimmune response in pediatric KTR. Therefore, regular dnDSA screening and close monitoring of graft function in case of BKPyV-DNAemia followed by subsequent reduction of immunosuppressive therapy are recommended.

Keywords: BK polyomavirus-associated nephropathy; Donor-specific antibodies; Kidney transplant rejection; Pediatric kidney transplantation.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • BK Virus* / immunology
  • BK Virus* / physiology
  • Child
  • Child, Preschool
  • Female
  • Graft Rejection* / epidemiology
  • Graft Rejection* / immunology
  • Graft Rejection* / virology
  • Graft Survival
  • HLA Antigens / immunology
  • Humans
  • Immunosuppression Therapy / adverse effects
  • Immunosuppression Therapy / methods
  • Immunosuppressive Agents / administration & dosage
  • Infant
  • Kidney Transplantation* / adverse effects
  • Longitudinal Studies
  • Male
  • Polyomavirus Infections* / complications
  • Polyomavirus Infections* / immunology
  • Polyomavirus Infections* / virology
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Tumor Virus Infections* / complications
  • Tumor Virus Infections* / immunology
  • Tumor Virus Infections* / virology
  • Virus Replication

Substances

  • HLA Antigens
  • Immunosuppressive Agents