Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance

Clin J Am Soc Nephrol. 2015 Jun 5;10(6):1041-9. doi: 10.2215/CJN.08710814. Epub 2015 May 15.

Abstract

Background and objectives: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids.

Design, setting, participants, & measurements: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies.

Results: Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction.

Conclusions: Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.

Keywords: acute allograft rejection; immunosuppression; kidney transplantation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adult
  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antigens, CD / immunology
  • Antigens, Neoplasm / immunology
  • Antilymphocyte Serum / adverse effects
  • Antilymphocyte Serum / therapeutic use*
  • CD52 Antigen
  • Calcineurin Inhibitors / adverse effects
  • Calcineurin Inhibitors / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Glycoproteins / antagonists & inhibitors
  • Glycoproteins / immunology
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Living Donors*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / therapeutic use*
  • Odds Ratio
  • Propensity Score
  • Proportional Hazards Models
  • Receptors, Interleukin-2 / antagonists & inhibitors
  • Receptors, Interleukin-2 / immunology
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Steroids / adverse effects
  • Steroids / therapeutic use*
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Time Factors
  • Tissue and Organ Procurement
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Antigens, Neoplasm
  • Antilymphocyte Serum
  • CD52 Antigen
  • CD52 protein, human
  • Calcineurin Inhibitors
  • Glycoproteins
  • Immunosuppressive Agents
  • Receptors, Interleukin-2
  • Steroids
  • Alemtuzumab
  • Mycophenolic Acid
  • Tacrolimus