title: Revisiting traditional risk factors for rejection and graft loss after kidney transplantation.
abstract: Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single-antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third-party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death-censored graft survival (DCGS) and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization.
authors.affiliation: Department of Surgerya, University of Minnesota, Minneapolis, MN, USA. dunn0017@umn.edu
authors.forename: T B
authors.initials: TB
authors.lastname: Dunn
authors.forename: H
authors.initials: H
authors.lastname: Noreen
authors.forename: K
authors.initials: K
authors.lastname: Gillingham
authors.forename: D
authors.initials: D
authors.lastname: Maurer
authors.forename: O G
authors.initials: OG
authors.lastname: Ozturk
authors.forename: T L
authors.initials: TL
authors.lastname: Pruett
authors.forename: R A
authors.initials: RA
authors.lastname: Bray
authors.forename: H M
authors.initials: HM
authors.lastname: Gebel
authors.forename: A J
authors.initials: AJ
authors.lastname: Matas
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016019:Survival Analysis; D014019:Tissue Donors
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents