Thymoglobulin dose optimization for induction therapy in high risk kidney transplant recipients

Transplantation. 2008 May 27;85(10):1425-30. doi: 10.1097/TP.0b013e31816dd596.

Abstract

Background: Thymoglobulin (rATG) has become the agent of choice for induction therapy in high immunological risk kidney transplant recipients. However, its optimal dosing in this subgroup has not been studied.

Methods: To evaluate the effect of total rATG dosing on graft outcomes in such patients, we conducted a retrospective cohort study of 96 adult patients who received repeat transplants (85%) or had panel reactive antibody more than 40% (19%) and were maintained on tacrolimus, mycophenolate mofetil, and steroid. Group 1 (n=33) received less than or equal to 7.5 and group 2 (n=63) received more than 7.5 mg/kg rATG. Graft and patient survival, incidence of acute rejection (AR), and 12-month serum creatinine (SCr) were examined.

Results: The groups were comparable regarding demographics, donor source, retransplantation, panel reactive antibody, and human leukocyte antigen mismatch. Group 2 had more African Americans (44.4% vs. 21.2%, P=0.03). During the 25.4+/-18.0 months follow-up graft survival was 82.5% and 79.4%, respectively (P=0.54). Three in group 1 and four in group 2 died (P=0.65). The incidence of biopsy proven AR during the first 12-months did not differ between the groups (9.5% vs. 8.8%, respectively, P=0.9). SCr at 12 months was 1.6+/-0.7 in group 1 and 1.8+/-1.0 in group 2 (P=0.3). There was no independent association between rATG dose and graft survival (hazard ratio: 0.85, P=0.79, 95% CI: 0.26-2.7 for group 2 vs. 1) or 1-year SCr (regression coefficient=0.02 for ln(SCr), P=0.3; 95%CI: -0.01 to 0.6).

Conclusion: Our results suggest that in high risk kidney transplant recipients total rATG doses less than or equal to 7.5 mg/kg are safe and effective in achieving a low rate of AR and graft outcomes comparable to higher doses.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Antilymphocyte Serum / therapeutic use
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus Infections / prevention & control
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / mortality
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis
  • Tacrolimus / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antilymphocyte Serum
  • Antiviral Agents
  • Immunosuppressive Agents
  • thymoglobulin
  • Prednisone
  • Tacrolimus