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.

Impact of pretransplant donor‐specific antibodies on kidney allograft recipients with negative flow cytometry cross‐matches

“…Many studies show that the risk of AR is higher in patients with than without pretransplant DSA, primarily due to ABMR . The 1‐year incidence of ABMR observed in the present study (11.1%) was comparable to those observed in recent studies, with ABMR in sensitized patients usually occurring within the first year after transplant .…”

“…Generally, desensitization based on DSA strength, expressed as mean fluorescence intensity (MFI), is thought to be required . However, other studies report that patients negative for pretransplant DSA on FCXM do not require desensitization therapy due to the minimal immunologic risk . The lack of consensus among these studies is due, at least in part, to the heterogeneity of induction regimens, desensitization protocols, and FCXM results.…”

“…The lack of consensus among these studies is due, at least in part, to the heterogeneity of induction regimens, desensitization protocols, and FCXM results. Similarly, studies evaluating the impact of DSA in FCXM‐negative patients used different induction agents and desensitization protocols …”

Out with the old, in with the new: Virtual versus physical crossmatching in the modern era

“…In most cases when confirming a true “false positive” due to denatured or cryptic antigens, transplantation is likely safe. However, in situations wherein the DSA identified by the SAB is a low titer HLA antibody, these situations can pose an increased risk for early graft rejection . It is important to discriminate between these two scenarios so that educated transplant decisions can be made and appropriate posttransplant therapies can be utilized.…”

Improved flow cytometry crossmatching in kidney transplantation

“…The results of some studies reporting clinical outcomes in patients with pretransplant DSA in the setting of negative FC‐XM were pooled in a meta‐analysis including a total of 145 patients with pretransplant DSA . An increased incidence of AMR (25% vs 11%) and a significant decrease in kidney graft survival in the presence of pretransplant DSA compared with patients without pretransplant DSA were observed.…”