title: Clinical Significance of Pretransplant Donor-Specific Antibodies in the Setting of Negative Cell-Based Flow Cytometry Crossmatching in Kidney Transplant Recipients.
abstract: Antibodies to donor-specific HLA antigens (donor-specific antibodies [DSA]) detected by single-antigen bead (SAB) analysis prior to kidney transplant have been associated with inferior graft outcomes. However, studies of pretransplant DSA, specifically in the setting of a negative flow cytometry crossmatch (FCXM) without desensitization therapy, are limited. Six hundred and sixty kidney and kidney-pancreas recipients with a negative pretransplant FCXM from September 2007 to August 2012 without desensitization therapy were analyzed with a median follow-up of 4.2 years. All patients underwent cell-based FCXM and SAB analysis on current and historic sera prior to transplantation. One hundred and sixty-two patients (24.5%) had DSA detected prior to transplant. One-year acute rejection rates were similar in DSA-positive versus DSA-negative patients (15.4% vs. 11.4%, respectively; p = 0.18) and were higher in those with DSA mean fluorescence intensity (MFI) greater than or equal to 3000 in multivariable analysis (p = 0.046). The estimated glomerular filtration rate (eGFR) at 3 and 4 years was lower in the DSA(+) versus the DSA(-) group (p = 0.050 at 3 years) without an impact on 5-year death-censored graft survival (89.0% vs. 90.6%, respectively; p = 0.53). Timing (current or historic) of DSA detection did not alter these findings. In conclusion, pretransplant DSA in the setting of a negative FCXM confers minimal immunologic risk in the intermediate term, does not necessitate desensitization therapy and should not represent a barrier to renal transplant.
authors.affiliation: Division of Renal Diseases and Hypertension, Transplant Center, University of Colorado, Denver, CO.
authors.forename: O O
authors.initials: OO
authors.lastname: Adebiyi
authors.affiliation: Department of Pediatrics, University of Colorado, Denver, CO.
authors.forename: J
authors.initials: J
authors.lastname: Gralla
authors.affiliation: Department of Pharmacy, University of Colorado, Denver, CO.
authors.forename: P
authors.initials: P
authors.lastname: Klem
authors.affiliation: Clinimmune Labs, University of Colorado, Denver, CO.
authors.forename: B
authors.initials: B
authors.lastname: Freed
authors.affiliation: Division of Renal Diseases and Hypertension, Transplant Center, University of Colorado, Denver, CO.
authors.forename: S
authors.initials: S
authors.lastname: Davis
authors.affiliation: Division of Renal Diseases and Hypertension, Transplant Center, University of Colorado, Denver, CO.
authors.forename: A C
authors.initials: AC
authors.lastname: Wiseman
authors.affiliation: Division of Renal Diseases and Hypertension, Transplant Center, University of Colorado, Denver, CO.
authors.forename: J E
authors.initials: JE
authors.lastname: Cooper
mesh_terms: D003888:Desensitization, Immunologic; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: alloantibody; clinical research/practice; crossmatch; graft survival; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; rejection: acute