title: Successful treatment of chronic antibody-mediated rejection with IVIG and rituximab in pediatric renal transplant recipients.
abstract: BACKGROUND
  Chronic antibody-mediated rejection (CAMR) of renal allografts has recently been recognized as a defined nosologic entity. The outcome of CAMR is poor; there is no established treatment protocol for this condition. We therefore initiated a pilot study on treatment of CAMR with an antihumoral regimen consisting of high-dose intravenous immunoglobulin (IVIG) and the chimeric anti-CD20 antibody rituximab.
  
  
  METHODS
  Six pediatric renal transplant recipients with CAMR received four weekly doses of IVIG (1 g/kg body weight per dose), followed by a single dose of rituximab (375 mg/m2 body surface area) 1 week after the last IVIG infusion. Renal allograft biopsies were evaluated using the Banff '05 classification. Human leukocyte antigen-specific antibodies were detected by panel-reactive lymphocytotoxicity and solid phase ELISA assays.
  
  
  RESULTS
  Median glomerular filtration rate during 6 months before intervention dropped by 25 (range, 11-26) mL/min/1.73 m2 (P<0.05) and increased in response to antihumoral therapy by 21 (-14 to +30) 6 months (P<0.05) and by 19 (-14 to +23) mL/min/1.73 m2 12 months (P=0.063) after start of treatment. Glomerular filtration rate improved or stabilized in 4 patients; the two nonresponders had the highest degree of transplant glomerulopathy, the highest degree of C4d deposition in peritubular capillaries and pronounced interstitial inflammation. The treatment regimen was well tolerated.
  
  
  CONCLUSIONS
  This pilot study demonstrates that CAMR in pediatric renal transplant recipients can be treated successfully and safely with a combination of IVIG and rituximab. This observation should encourage more extensive studies to evaluate this new treatment strategy.
authors.affiliation: Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Billing
authors.forename: Susanne
authors.initials: S
authors.lastname: Rieger
authors.forename: Jörg
authors.initials: J
authors.lastname: Ovens
authors.forename: Caner
authors.initials: C
authors.lastname: Süsal
authors.forename: Anette
authors.initials: A
authors.lastname: Melk
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Waldherr
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tönshoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D002648:Child; D015935:Complement C4b / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010865:Pilot Projects; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D010446:Peptide Fragments; D000069283:Rituximab; D015935:Complement C4b; C032261:complement C4d