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.