title: Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin.
abstract: BACKGROUND
  Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients.
  
  
  METHODS
  A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses.
  
  
  RESULTS
  Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups.
  
  
  CONCLUSIONS
  Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.
authors.affiliation: Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224, USA. mai.martin@mayo.edu
authors.forename: Martin L
authors.initials: ML
authors.lastname: Mai
authors.forename: Nasimul
authors.initials: N
authors.lastname: Ahsan
authors.forename: Hani M
authors.initials: HM
authors.lastname: Wadei
authors.forename: Petrina V
authors.initials: PV
authors.lastname: Genco
authors.forename: Xochiquetzal J
authors.initials: XJ
authors.lastname: Geiger
authors.forename: Darrin L
authors.initials: DL
authors.lastname: Willingham
authors.forename: C Burcin
authors.initials: CB
authors.lastname: Taner
authors.forename: Winston R
authors.initials: WR
authors.lastname: Hewitt
authors.forename: Hani P
authors.initials: HP
authors.lastname: Grewal
authors.forename: Justin H H
authors.initials: JH
authors.lastname: Nguyen
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Hughes
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Gonwa
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000097:blood*; D000918:Antibody Specificity; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D003601:Cytotoxicity Tests, Immunologic; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D012189:Retrospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D000961:Antilymphocyte Serum; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents