Impact of Pre Transplant Donor Specific Antibodies in the Setting of a Negative Cell Based Flow Cytometry Cross Match On Graft Outcomes.

Abstract

Background:Presence of antibodies to donor specific HLA antigens (DSA) detected by single antigen bead (SAB) analysis prior to kidney transplant has been associated with inferior graft outcomes. However, it is unclear if low-level DSA (e.g. in a negative flow cytometry crossmatch (FCXM)) leads to a higher risk of rejection or a later graft dysfunction. Most studies,limited by small sample size, have not considered flow cytometry cross match results in the analysis. Methods: 547 consecutive recipients of a first kidney or kidney/pancreas transplant with a negative pre-transplant FCXM between September 2007 and August 2012 at our center were analyzed. All patients underwent cell-based FCXM and SAB analysis (LABScreen beads, One Lambda Inc.) on current and historic sera prior to transplantation. Patients were placed on triple immunosuppression. Graft outcomes were compared for patients with (DSA+) and without (DSA-) pre-transplant DSA. Results: Of 547 patients with negative pre-transplant FCXM, 196 had DSA (MFI ≥ 500) detected prior to transplant by SAB analysis. Acute rejection (AR) rates at one year were similar in DSA+ vs. DSA- (15% vs. 12% respectively, p=0.22) although AR occurred earlier in the DSA+ group. With median follow up period of 2.3 years, mean GFR and mean proteinuria (0.27 g/day vs 0.35 g/day for DSA+ vs. DSA- groups) was similar for both groups. Three year graft survival by Kaplan-Meier estimate was similar in DSA+ and DSA-patients (p= 0.81) and remained similar when defining DSA as MFI ≥ 1000.Figure: No Caption available.Conclusion: To date, this is the largest series characterizing post-transplant outcomes of patients with pre-transplant +DSA/-FCXM without desensitization therapies. Presence of pre-transplant DSA in the setting of negative FCXM was neither associated with higher AR rates nor with longer term graft outcomes. These data suggest that DSA detected by SAB alone may confer minimal immunologic risk and do not require preemptive B-cell/antibody-targeted therapies.