Conversion From Calcineurin Inhibitors to Belatacept in HLA-sensitized Kidney Transplant Recipients With Low-level Donor-specific Antibodies

Transplantation. 2019 Oct;103(10):2150-2156. doi: 10.1097/TP.0000000000002592.

Abstract

Background: Belatacept could be the treatment of choice in renal-transplant recipients with renal dysfunction attributed to calcineurin inhibitor (CNI) nephrotoxicity. Few studies have described its use in patients with donor-specific antibody (DSA).

Methods: We retrospectively evaluated conversion from CNIs to belatacept in 29 human leukocyte antigen-immunized renal-transplant recipients. Data about acute rejection, DSA, and renal function were collected. These patients were compared with 42 nonimmunized patients treated with belatacept.

Results: Patients were converted from CNIs to belatacept a median of 444 days (interquartile range, 85-1200) after transplantation and were followed up after belatacept conversion, for a median of 308 days (interquartile range, 125-511). At conversion, 16 patients had DSA. Nineteen DSA were observed in these 16 patients, of which 11/19 were <1000 mean fluorescence intensity (MFI), 7/19 were between 1000 and 3000 MFI, and one was >3000 MFI. At last follow-up, preexisting DSA had decreased or stabilized. Seven patients still had DSA with a mean MFI of 1298 ± 930 at the last follow-up. No patient developed a de novo DSA in the DSA-positive group. In the nonimmunized group, one patient developed de novo DSA (A24-MFI 970; biopsy for cause did not show biopsy-proven acute rejection or microinflammation score). After belatacept conversion, one antibody-mediated rejection was diagnosed. The mean estimated glomerular filtration rate improved from 31.7 ± 14.2 mL/min/1.73 m to 40.7 ± 12.3 mL/min/1.73 m (P < 0.0001) at 12 months after conversion. We did not find any significant difference between groups in terms of renal function, proteinuria, or biopsy-proven acute rejection.

Conclusions: We report on a safe conversion to belatacept in human leukocyte antigen-immunized patients with low DSA levels.

MeSH terms

  • Abatacept / administration & dosage*
  • Adult
  • Aged
  • Allografts / drug effects
  • Allografts / immunology
  • Allografts / pathology
  • Biopsy
  • Calcineurin Inhibitors / administration & dosage
  • Calcineurin Inhibitors / adverse effects*
  • Drug Substitution
  • Female
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / immunology
  • Graft Rejection / blood
  • Graft Rejection / drug therapy*
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • HLA Antigens / immunology
  • Humans
  • Isoantibodies / blood*
  • Isoantibodies / immunology
  • Isoantigens / immunology
  • Kidney / drug effects
  • Kidney / immunology
  • Kidney / pathology
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Renal Insufficiency / chemically induced
  • Renal Insufficiency / prevention & control*
  • Treatment Outcome

Substances

  • Calcineurin Inhibitors
  • HLA Antigens
  • Isoantibodies
  • Isoantigens
  • Abatacept