title: Successful renal transplantation across simultaneous ABO incompatible and positive crossmatch barriers.
abstract: ABO incompatibility and human leukocyte antigen (HLA) sensitization remain the two largest barriers to optimal utilization of kidneys from live donors. Here we describe the first successful transplantation of patients who were both ABO incompatible and crossmatch positive with their only available donor. A preconditioning regimen of plasmapheresis (PP) and low-dose CMV hyperimmune globulin (CMVIg) was delivered every other day until donor-specific antibody (DSA) titers were reduced to a safe level and isoagglutinin titers were < or =16. Each patient received quadruple sequential immunosuppression, splenectomy and three protocol post-transplant PP/CMVIg treatments. There was no hyperacute rejection. Two of the three patients had a persistent positive cytotoxic crossmatch on the day of transplant and eliminated their DSA subsequently. Antibody-mediated rejection (AMR) in one patient was reversed by reinitiating PP/CMVIg and anti-CD20. The patients are more than 9 months post-transplant with excellent graft function. Preconditioning with PP/CMVIg results in a durable suppression of DSA and permits accommodation of the allograft to a discordant blood type. The ability to cross these two barriers simultaneously is clinically important as sensitized patients have often exhausted their blood type compatible living donors during previous transplants.
authors.affiliation: The Department of Surgery, The Johns Hopkins University School of Medicine, Balitmore, Maryland, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Warren
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Zachary
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sonnenday
authors.forename: Karen E
authors.initials: KE
authors.lastname: King
authors.forename: Matthew
authors.initials: M
authors.lastname: Cooper
authors.forename: Lloyd E
authors.initials: LE
authors.lastname: Ratner
authors.forename: R Sue
authors.initials: RS
authors.lastname: Shirey
authors.forename: Mark
authors.initials: M
authors.lastname: Haas
authors.forename: Mary S
authors.initials: MS
authors.lastname: Leffell
authors.forename: Robert A
authors.initials: RA
authors.lastname: Montgomery
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D000906:Antibodies / Q000737:chemistry; D018951:Antigens, CD20 / Q000737:chemistry; D001787:Blood Group Incompatibility; D001788:Blood Grouping and Crossmatching; D005260:Female; D006085:Graft Survival; D006650:Histocompatibility Testing; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000628:therapy; D016030:Kidney Transplantation / Q000379:methods*; D007700:Kinetics; D019520:Living Donors; D010956:Plasmapheresis / Q000379:methods; D013997:Time Factors
chemical_list: D000017:ABO Blood-Group System; D000906:Antibodies; D018951:Antigens, CD20; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents