title: Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Division of Nephrology, bekir.tanriover@utsouthwestern.edu.
authors.forename: Bekir
authors.initials: B
authors.lastname: Tanriover
authors.affiliation: Department of Clinical Sciences, and.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center for Abdominal Organ Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas;
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacConmara
authors.affiliation: Department of Clinical Sciences, and.
authors.forename: Ang
authors.initials: A
authors.lastname: Gao
authors.affiliation: Booth School of Business, University of Chicago, Illinois;
authors.forename: Burhaneddin
authors.initials: B
authors.lastname: Sandikci
authors.affiliation: Information Systems, University of Texas, Dallas, Texas;
authors.forename: Mehmet U S
authors.initials: MU
authors.lastname: Ayvaci
authors.affiliation: Computer Science and Information Systems, Texas A&M University, Commerce, Texas;
authors.forename: Mutlu
authors.initials: M
authors.lastname: Mete
authors.affiliation: Division of Pharmacy, New York Presbyterian Hospital, New York, New York; and.
authors.forename: Demetra
authors.initials: D
authors.lastname: Tsapepas
authors.affiliation: Division of Nephrology.
authors.forename: Nilum
authors.initials: N
authors.lastname: Rajora
authors.affiliation: Division of Nephrology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Prince
authors.initials: P
authors.lastname: Mohan
authors.affiliation: Division of Nephrology.
authors.forename: Ronak
authors.initials: R
authors.lastname: Lakhia
authors.affiliation: Division of Nephrology.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Division of Nephrology.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vazquez
mesh_terms: D000208:Acute Disease; D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D000074301:CD52 Antigen; D065095:Calcineurin Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D019520:Living Donors; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D016017:Odds Ratio; D057216:Propensity Score; D016016:Proportional Hazards Models; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D013256:Steroids / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D009927:Tissue and Organ Procurement; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000961:Antilymphocyte Serum; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D065095:Calcineurin Inhibitors; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D013256:Steroids; D000074323:Alemtuzumab; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: acute allograft rejection; immunosuppression; kidney transplantation