Sensitization from transfusion in patients awaiting primary kidney transplant

Abstract

Background: Sensitization to human leukocyte antigen (HLA) from red blood cell (RBC) transfusion is poorly quantified and is based on outdated, insensitive methods. The objective was to evaluate the effect of transfusion on the breadth, magnitude and specificity of HLA antibody formation using sensitive and specific methods.

Methods: Transfusion, demographic and clinical data from the US Renal Data System were obtained for patients on dialysis awaiting primary kidney transplant who had ≥ 2 HLA antibody measurements using the Luminex single-antigen bead assay. One cohort included patients with a transfusion (n = 50) between two antibody measurements matched with up to four nontransfused patients (n = 155) by age, sex, race and vintage (time on dialysis). A second crossover cohort (n = 25) included patients with multiple antibody measurements before and after transfusion. We studied changes in HLA antibody mean fluorescence intensity (MFI) and calculated panel reactive antibody (cPRA).

Results: In the matched cohort, 10 of 50 (20%) transfused versus 6 of 155 (4%) nontransfused patients had a ≥ 10 HLA antibodies increase of >3000 MFI (P = 0.0006); 6 of 50 (12%) transfused patients had a ≥ 30 antibodies increase (P = 0.0007). In the crossover cohort, the number of HLA antibodies increasing >1000 and >3000 MFI was higher in the transfused versus the control period, P = 0.03 and P = 0.008, respectively. Using a ≥ 3000 MFI threshold, cPRA significantly increased in both matched (P = 0.01) and crossover (P = 0.002) transfused patients.

Conclusions: Among prospective primary kidney transplant recipients, RBC transfusion results in clinically significant increases in HLA antibody strength and breadth, which adversely affect the opportunity for future transplant.

Keywords: HLA antibody; calculated panel reactive antibody; kidney transplantation; sensitization; transfusion.

FIGURE 1:

Study population and schema for matched and crossover cohorts according to transfused versus nontransfused groups.

FIGURE 2:

Change in MFI for each unique HLA antibody identified in all patients included in both transfused and matched nontransfused groups (a and b) and crossover cohorts (c and d). The P-values presented in a and b are based on Pearson χ² analyses comparing the proportion of patients in the transfused and nontransfused groups with >10 (versus <10) HLA antibodies increasing >1000 MFI (a) and >3000 MFI (b). The P-values presented in c and d are based on Sign tests comparing the number of HLA antibodies increasing >1000 MFI (c) and >3000 MFI (d) during the transfused and control periods.

FIGURE 3:

Absolute change in cPRA levels for all patients in transfused and matched nontransfused groups (a and b) and crossover cohorts (c and d). The P-values presented in a and b are based on Pearson χ² analyses comparing the distribution of cPRA changes in the transfused and nontransfused groups using >1000 MFI (a) and >3000 MFI (b) as the threshold for defining an unacceptable antigen. The P-values presented in c and d are based on Sign tests comparing the change in cPRA during the transfused and control periods using >1000 MFI (c) and >3000 MFI (d) as the threshold for defining an unacceptable antigen.

FIGURE 4:

Change in MFI for each unique HLA antibody identified in all patients included in transfused and matched nontransfused groups (a and b) and crossover cohorts (c and d) excluding patients with proinflammatory events. The P-values presented in a and b are based on Pearson χ² analyses comparing the proportion of patients in the transfused and nontransfused groups with >10 (versus <10) HLA antibodies increasing >1000 MFI (a) and >3000 MFI (b). The P-values presented in c and d are based on Sign tests comparing the number of HLA antibodies increasing >1000 MFI (c) and >3000 MFI (d) during the transfused and control periods.