title: Donor Specificity but Not Broadness of Sensitization Is Associated With Antibody-Mediated Rejection and Graft Loss in Renal Allograft Recipients.
abstract: Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the "calculated population-reactive antibodies" (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor-specific HLA antibodies (DSA). Five hundred twenty-seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1-50% (n = 129), cPRA 51-100% (n = 43), and DSA (n = 105). Patients without DSA were considered as normal risk and received standard immunosuppression without T cell-depleting induction. Patients with DSA received an enhanced induction therapy and maintenance immunosuppression. Surveillance biopsies were performed at 3 and 6 months. Median follow-up was 5.7 years. Among the three cPRA groups, there were no differences regarding the 1-year incidence of ABMR (p = 0.16) and TCMR (p = 0.75). The 5-year allograft survival rates were similar and around 87% (p = 0.28). The estimated glomerular filtration rate at last follow-up was 50-53 mL/min (p = 0.45). On multivariable Cox proportional hazard analysis, the strongest independent predictor for ABMR and (death-censored) graft survival was pretransplantation DSA. cPRA were not predictive for ABMR, TCMR, or (death-censored) graft survival. We conclude that with current DSA assignment, the broadness of sensitization measured by cPRA does not imply an immunological risk.
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Wehmeier
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.|HLA-Diagnostic and Immunogenetics, Department of Laboratory Medicine, University Hospital Basel, Basel, Switzerland.|Transplantation Immunology and Nephrology, Department of Biomedicine, University Basel, Basel, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Hönger
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Cun
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.|HLA-Diagnostic and Immunogenetics, Department of Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Amico
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Hirt-Minkowski
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Georgalis
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Hopfer
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Dickenmann
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Steiger
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.|HLA-Diagnostic and Immunogenetics, Department of Laboratory Medicine, University Hospital Basel, Basel, Switzerland.|Transplantation Immunology and Nephrology, Department of Biomedicine, University Basel, Basel, Switzerland.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-9170-1341
authors.initials: S
authors.lastname: Schaub
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D015994:Incidence; D007518:Isoantibodies / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: clinical research/practice; histocompatibility; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; major histocompatibility complex (MHC); panel reactive antibody (PRA); risk assessment/risk stratification