title: Alemtuzumab induction and recurrence of glomerular disease after kidney transplantation.
abstract: BACKGROUND
  An increase in the incidence of autoimmune diseases has been described in patients receiving alemtuzumab.
  
  
  METHODS
  To determine whether induction with alemtuzumab increases recurrence of glomerular disease, we performed a retrospective study in 443 patients with biopsy-proven glomerular diseases undergoing kidney transplantation. Patients receiving alemtuzumab (n=161) were compared with those receiving interleukin (IL)-2-receptor antagonists (n=217) or antithymocyte globulin (n=64).
  
  
  RESULTS
  Biopsy-proven glomerular disease recurrence was similar in patients induced with alemtuzumab or IL-2 receptor antagonists. Patients receiving antithymocyte antibody had a lower recurrence rate than patients treated with other induction agents, with borderline significance (hazard ratio [HR] 0.13, 95% confidence interval [95% CI] 0.02-0.98, P=0.047). Patients with systemic lupus treated with alemtuzumab had a similar re-emergence of autoreactive antibodies to patients treated with other agents. Recurrent disease increased the risk of allograft failure (HR 2.36, 95% CI 1.28-4.32, P=0.0056). The development of acute rejection and the use of deceased (vs. living) donor kidneys were also significant factors influencing graft survival. A greater risk of mortality was detected in those patients with recurrent glomerular disease (HR 3.76, 95% CI 1.37-10.35, P=0.01), whereas increased age at transplantation (HR 1.05) and the use of deceased (vs. living) donor kidneys (HR 3.20) also increased mortality. No specific induction agent significantly affected graft loss or mortality when using adjusted or unadjusted hazard ratios.
  
  
  CONCLUSIONS
  In this retrospective analysis, induction with alemtuzumab did not increase the rate of re-emergence of autoantibodies or biopsy-proven recurrence of glomerular disease. A slight reduction in the incidence of recurrence was observed in patients treated with thymoglobulin, yet this observation can only be validated in a prospective randomized trial.
authors.affiliation: Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI 53713, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Mezrich
authors.forename: Arjang
authors.initials: A
authors.lastname: Djamali
authors.forename: Glen
authors.initials: G
authors.lastname: Leverson
authors.forename: L Thomas
authors.initials: LT
authors.lastname: Chin
authors.forename: José
authors.initials: J
authors.lastname: Torrealba
authors.forename: Debra
authors.initials: D
authors.lastname: Bloom
authors.forename: Barbara
authors.initials: B
authors.lastname: Voss
authors.forename: Bryan N
authors.initials: BN
authors.lastname: Becker
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Knechtle
authors.forename: Hans W
authors.initials: HW
authors.lastname: Sollinger
authors.forename: John D
authors.initials: JD
authors.lastname: Pirsch
authors.forename: Milagros D
authors.initials: MD
authors.lastname: Samaniego
mesh_terms: D000328:Adult; D000367:Age Factors; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects* / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000209:etiology / Q000401:mortality / Q000601:surgery*; D007678:Kidney Glomerulus; D016030:Kidney Transplantation; D019520:Living Donors; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D018570:Risk Assessment; D055502:Secondary Prevention; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D015375:Receptors, Interleukin-2; D000074323:Alemtuzumab