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Donor Specificity but Not Broadness of Sensitization Is Associated With Antibody‐Mediated Rejection and Graft Loss in Renal Allograft Recipients
Authors:C. Wehmeier  G. Hönger  H. Cun  P. Amico  P. Hirt‐Minkowski  A. Georgalis  H. Hopfer  M. Dickenmann  J. Steiger  S. Schaub
Affiliation:1. Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland;2. HLA‐Diagnostic and Immunogenetics, Department of Laboratory Medicine, University Hospital Basel, Basel, Switzerland;3. Transplantation Immunology and Nephrology, Department of Biomedicine, University Basel, Basel, Switzerland;4. Institute for Pathology, University Hospital Basel, Basel, Switzerland
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.
Keywords:clinical research/practice  histocompatibility  kidney transplantation/nephrology  kidney (allograft) function/dysfunction  major histocompatibility complex (MHC)  panel reactive antibody (PRA)  risk assessment/risk stratification
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