title: High dose intravenous immunoglobulin therapy for donor-specific antibodies in kidney transplant recipients with acute and chronic graft dysfunction.
abstract: BACKGROUND
  Postkidney transplant donor-specific antibodies (DSA) have been identified as important contributors to graft loss. Few therapeutic options exist and have been met with limited success. We report outcomes in patients with de novo DSA and graft damage treated with a protocol of high-dose intravenous immunoglobulin (IVIG).
  
  
  METHODS
  Retrospective analysis of 28 kidney transplant recipients with de novo DSA and graft damage in the form of either chronic graft dysfunction (group 1, n=20) or a recent previous acute antibody-mediated rejection (AMR) episode (group 2, n=8) prescribed a standard regimen of high-dose (5 g/kg) IVIG dosed over 6 months.
  
  
  RESULTS
  Mean fluorescence intensity (MFI) of 70 total DSA decreased by 12%at the end of treatment (T1, P=0.14) and by 18%at last follow up (T2, P=0.035) compared with treatment initiation (T0) MFI. The most robust effect was seen in class I DSA (37% decrease at T2 versus T0, P=0.05) and in DSA from patients in group 2 (52% decrease at T2 versus T0, P=0.008). Graft function stabilized in patients in group 2 but continued to decline in those in group 1.
  
  
  CONCLUSIONS
  High-dose IVIG resulted in modest DSA MFI reductions in patients with previous graft damage, with a larger effect occurring in class I DSA in patients with a previous acute AMR. There was no clinical treatment benefit in patients with ongoing chronic graft damage, whereas high-dose IVIG may reduce the risk of chronic graft dysfunction in those with an acute AMR event.
authors.affiliation: 1 Division of Renal Diseases and Hypertension, Transplant Center, University of Colorado Denver, CO. 2 Department of Pediatrics, University of Colorado Denver, CO. 3 Department of Pharmacy, University of Colorado Denver, CO. 4 Address correspondence to: James E. Cooper, Transplant Center, University of Colorado Denver, Mail Stop F749, AOP 7089, 1635 North Aurora Court, Aurora, CO 80045.
authors.forename: James E
authors.initials: JE
authors.lastname: Cooper
authors.forename: Jane
authors.initials: J
authors.lastname: Gralla
authors.forename: Patrick
authors.initials: P
authors.lastname: Klem
authors.forename: Laurence
authors.initials: L
authors.lastname: Chan
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Wiseman
mesh_terms: D000208:Acute Disease; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects*; D006648:Histocompatibility; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies