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

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 cro...

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Bibliographic Details
Published in:American journal of transplantation 2016-12, Vol.16 (12), p.3458-3467
Main Authors: Adebiyi, O. O., Gralla, J., Klem, P., Freed, B., Davis, S., Wiseman, A. C., Cooper, J. E.
Format: Article
Language:English
Subjects:
alloantibody
clinical research/practice
Clinical significance
crossmatch
Desensitization, Immunologic
Female
Flow cytometry
Flow Cytometry - methods
Follow-Up Studies
Glomerular Filtration Rate
Graft Rejection - immunology
graft survival
Graft Survival - immunology
Histocompatibility Testing - methods
HLA Antigens - immunology
Humans
Immunoglobulins
Immunology
Isoantibodies - immunology
kidney (allograft) function/dysfunction
Kidney Failure, Chronic - immunology
Kidney Failure, Chronic - surgery
Kidney Function Tests
Kidney Transplantation
kidney transplantation/nephrology
Kidney transplants
Male
Middle Aged
Prognosis
rejection: acute
Retrospective Studies
Risk Factors
Tissue Donors
Transplant Recipients
Transplants & implants
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Summary: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. In this retrospective study, the authors report minimal risk to intermediate‐term graft outcomes in nondesensitized kidney recipients with flow cytometry crossmatch‐negative pretransplant donor‐specific antibodies, and suggest these antibodies do not warrant desensitization and should not preclude transplantation.
ISSN:1600-6135
1600-6143
DOI:10.1111/ajt.13848