A CD3+ count-based thymoglobulin induction regimen permits delayed introduction of calcineurin inhibitors in kidney transplantation

Clin Transplant. 2012 Nov-Dec;26(6):900-9. doi: 10.1111/j.1399-0012.2012.01656.x. Epub 2012 Jun 4.

Abstract

Background: Withholding calcineurin inhibitors (CNIs) can be considered when graft function is inadequate following kidney transplantation (KT). Thymoglobulin (rATG) can be used to prevent acute rejection while CNIs are being withheld. Here, we report our results of a novel CNI-sparing induction protocol, which utilizes a CD3+ cell count-based rATG treatment regimen when delayed graft function (DGF) develops in the immediate postoperative period.

Methods: In a cohort of 153 consecutive deceased-donor KT recipients, all received a single intraoperative dose of basiliximab; 84 subsequently developed DGF and therefore received rATG (rATG+ group), while 69 demonstrated immediate graft function and received CNIs (rATG- group).

Results: In the rATG+ group, mean duration of therapy was 8.5±6.0 d, permitting CNI initiation to be delayed until postoperative day 10.3±6.2. Cumulative dose of rATG was only 5.1±4.5 mg/kg while targeting CD3+ counts of ≤30 cells/mm3. CD3+ counts were reduced to a mean of 16.7±17.0 cells/mm3 during therapy. At one yr, patient and graft survival rates were 97.6% and 92.9%, respectively, while the frequency of infections and malignancies were not significantly increased compared to the rATG- group.

Conclusion: A unique induction regimen successfully delayed CNI initiation by using modest doses of rATG to deplete CD3+ cells, while yielding excellent long-term graft outcome without increased risk of infection or malignancy.

Publication types

  • Clinical Trial

MeSH terms

  • Antibodies, Monoclonal
  • Antilymphocyte Serum / therapeutic use*
  • Basiliximab
  • CD3 Complex / metabolism*
  • Calcineurin / administration & dosage
  • Calcineurin Inhibitors*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Kidney Diseases / surgery*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Prognosis
  • Recombinant Fusion Proteins
  • Recombinant Proteins / therapeutic use*
  • Retrospective Studies
  • Risk Factors
  • Survival Rate

Substances

  • Antibodies, Monoclonal
  • Antilymphocyte Serum
  • CD3 Complex
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Basiliximab
  • thymoglobulin
  • Calcineurin