Safe Conversion From Tacrolimus to Belatacept in High Immunologic Risk Kidney Transplant Recipients With Allograft Dysfunction

Am J Transplant. 2015 Oct;15(10):2726-31. doi: 10.1111/ajt.13322. Epub 2015 May 18.

Abstract

There is no literature on the use of belatacept for sensitized patients or regrafts in kidney transplantation. We present our initial experience in high immunologic risk kidney transplant recipients who were converted from tacrolimus to belatacept for presumed acute calcineurin inhibitor (CNI) toxicity and/or interstitial fibrosis/tubular atrophy. Six (mean age = 40 years) patients were switched from tacrolimus to belatacept at a median of 4 months posttransplant. Renal function improved significantly from a peak mean estimated glomerular filtration rate (eGFR) of 23.8 ± 12.9 mL/min/1.73 m(2) prior to the switch to an eGFR of 42 ± 12.5 mL/min/1.73 m(2) (p = 0.03) at a mean follow-up of 16.5 months postconversion. No new rejection episodes were diagnosed despite a prior history of rejection in 2/6 (33%) patients. Surveillance biopsies performed in 5/6 patients did not show subclinical rejection. No development of donor-specific antibodies (DSA) was noted. In this preliminary investigation, we report improved kidney function without a concurrent increase in risk of rejection and DSA in six sensitized patients converted from tacrolimus to belatacept. Improvement in renal function was noted even in patients with chronic allograft fibrosis without evidence of acute CNI toxicity. Further studies with protocol biopsies are needed to ensure safety and wider applicability of this approach.

Keywords: Calcineurin inhibitor (CNI); fusion proteins and monoclonal antibodies: belatacept, drug toxicity, immunosuppressant; immunosuppressant; interstitial fibrosis and tubular atrophy; sensitization.

MeSH terms

  • Abatacept / therapeutic use*
  • Adult
  • Aged
  • Allografts / drug effects
  • Allografts / physiopathology
  • Female
  • Follow-Up Studies
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Postoperative Complications / chemically induced*
  • Renal Insufficiency / chemically induced*
  • Retrospective Studies
  • Tacrolimus / adverse effects*
  • Tacrolimus / therapeutic use
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Abatacept
  • Tacrolimus