title: Root cause analysis of limitations of virtual crossmatch for kidney allocation to highly-sensitized patients.
abstract: Efficient allocation of deceased donor organs depends upon effective prediction of immunologic compatibility based on donor HLA genotype and recipient alloantibody profile, referred to as virtual crossmatching (VCXM). VCXM has demonstrated utility in predicting compatibility, though there is reduced efficacy for patients highly sensitized against allogeneic HLA antigens. The recently revised deceased donor kidney allocation system (KAS) has increased transplantation for this group, but with an increased burden for histocompatibility testing and organ sharing. Given the limitations of VCXM, we hypothesized that increased organ offers for highly-sensitized patients could result in a concomitant increase in offers rejected due to unexpectedly positive crossmatch. Review of 645 crossmatches performed for deceased donor kidney transplantation at our center did not reveal a significant increase in positive crossmatches following KAS implementation. Positive crossmatches not predicted by VCXM were concentrated among highly-sensitized patients. Root cause analysis of VCXM failures identified technical limitations of anti-HLA antibody testing as the most significant contributor to VCXM error. Contributions of technical limitations including additive/synergistic antibody effects, prozone phenomenon, and antigens not represented in standard testing panels, were evaluated by retrospective testing. These data provide insight into the limitations of VCXM, particularly those affecting allocation of kidneys to highly-sensitized patients.
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, United States.
authors.forename: Vivek
authors.initials: V
authors.lastname: Jani
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA, United States.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ingulli
authors.affiliation: Department of Surgery, University of California San Diego, La Jolla, CA, United States.
authors.forename: Kristen
authors.initials: K
authors.lastname: Mekeel
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, United States. Electronic address: gpmorris@ucsd.edu.
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Morris
mesh_terms: D001788:Blood Grouping and Crossmatching; D005838:Genotype; D006084:Graft Rejection / Q000175:diagnosis* / Q000517:prevention & control; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007114:Immunization; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation; D012189:Retrospective Studies; D060891:Root Cause Analysis; D014019:Tissue Donors; D009927:Tissue and Organ Procurement
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: Anti-HLA antibodies; Deceased donor kidney transplantation; Virtual crossmatch