Protocol Biopsies in Patients With Subclinical De Novo Donor-specific Antibodies After Kidney Transplantation: A Multicentric Study

Transplantation. 2020 Aug;104(8):1726-1737. doi: 10.1097/TP.0000000000003055.

Abstract

Background: De novo donor-specific antibodies (DSAs) are associated with antibody-mediated rejection (AMR) and allograft loss. Whether monitoring of de novo DSA (dnDSA) paired with systematic kidney biopsy should become routine remains to be established.

Methods: A retrospective multicentric study (9 French kidney transplant units of the Spiesser group) included patients without graft dysfunction biopsied because of the presence of dnDSA (One Lambda, mean fluorescence intensity [MFI], >1000).

Results: One hundred twenty-three patients (85 male/38 female; mean age, 49.5 ± 13.1 y old) were biopsied after the detection of a dnDSA, 65.3 months (median) after kidney transplantation. Graft function was stable within 3 months before biopsy (estimated glomerular filtration rate, 55.3 ± 18.9 mL/min/1.73 m). Fifty-one subclinical AMRs (sAMRs) (41.4%) were diagnosed, of which 32 (26%) active and 19 (15.5%) chronic active sAMR. Seventy-two biopsies revealed no AMR (58.5%). Predictive factors associated with the diagnosis of active sAMR were MFI of immunodominant DSA >4000, MFI of the sum of DSA >6300, age of the recipient <45 years old, and the absence of steroids at biopsy. The presence of proteinuria >200 mg/g was predictive of chronic active sAMR. The decrease of estimated glomerular filtration rate at 5 years post-biopsy was significantly higher in patients with acute sAMR (-25.2 ± 28.3 mL/min/1.73 m) and graft survival significantly lower.

Conclusions: Performing a kidney graft biopsy for the occurrence of dnDSA without renal dysfunction leads to the diagnosis of a sAMR in over 40% of cases. Nevertheless, we did not observe any effect of standard treatment in acute sAMR.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Allografts
  • Biopsy
  • Clinical Protocols*
  • Female
  • Follow-Up Studies
  • Graft Rejection / blood
  • Graft Rejection / diagnosis*
  • Graft Rejection / immunology
  • Graft Rejection / therapy
  • Graft Survival / immunology
  • HLA Antigens / immunology
  • Histocompatibility Testing / standards
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Isoantibodies / blood*
  • Isoantibodies / immunology
  • Kidney
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transplantation, Homologous / adverse effects
  • Treatment Outcome

Substances

  • HLA Antigens
  • Immunosuppressive Agents
  • Isoantibodies