Clinical Significance of Pretransplant Donor-Specific Antibodies in the Setting of Negative Cell-Based Flow Cytometry Crossmatching in Kidney Transplant Recipients

Am J Transplant. 2016 Dec;16(12):3458-3467. doi: 10.1111/ajt.13848. Epub 2016 Jun 15.

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.

Keywords: alloantibody; clinical research/practice; crossmatch; graft survival; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; rejection: acute.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Desensitization, Immunologic
  • Female
  • Flow Cytometry / methods*
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / immunology*
  • Graft Survival / immunology*
  • HLA Antigens / immunology
  • Histocompatibility Testing / methods*
  • Humans
  • Isoantibodies / immunology*
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Tissue Donors*
  • Transplant Recipients

Substances

  • HLA Antigens
  • Isoantibodies