Pretransplant Donor-Specific Anti-HLA Antibodies and Their Characteristics Are Associated With Poorer Kidney Graft Outcomes in Kidney and Kidney-Pancreas Recipients.

Abstract

The role of donor-specific antibodies (DSA) and their characteristics in kidney transplantation remains not fully understood. We aimed to analyze in a cohort of kidney and kidney-pancreas transplant recipients the effect of pretransplant DSA in kidney graft adverse outcomes: acute humoral rejection (AHR) and graft failure (GF). A cohort of 434 patients (pts) that received a kidney graft (67 pts also receiving a pancreas graft) between 2008-12 after a negative CDC crossmatch (XM) were included. Presence of anti-human leukocyte antigen (HLA) antibodies was investigated in pretransplant sera using a Luminex® screening assay and anti-HLA specificities were assigned performing a Luminex® single antigen assay [positive: mean fluorescence intensity (MFI) was ≥1000 (1K)]. In DSA+ pts, ROC curves were constructed to assess the ability of MFI values (DSAmax: highest DSA bead; DSAcum: detected DSA MFI sum) to predict AHR. Comparison between DSA defined groups:Table: No Caption available.1-year incidence of AHR by DSA class was 17%, 57% and 57%, in I (n=23), II (n=7) and I+II (n=7), respectively (logrank p=0.023); by DSA MFI was 6%, 46% and 67%, in 1k-3k (n=17), 3k-7k (n=11) and >7K (n=9), respectively (logrank p<0.001). Considering only DSA+ pts, comparisons were performed using χ2 or Mann-Whitney U test between AHR- (n=25) and AHR+ (n=12) groups. Differences were found in mean HLA mismatch (3.5 vs 4.3; p=0.008), median DSA number (1 vs 3; p=0.005), MFI DSAmax (2.5K vs 8K; p=0.001), DSAcum (3.5K vs 19.5K, p=0.001), DSAmax class II (12% vs 58%; p=0.006) and DSA class (AHR-: I 76%, II 12%, I+II 12%; p=0.02); number of kidney-pancreas (2 vs 2; p=0.6) and flow XM+ pts (2 vs 3; p=0.3) were similar. In ROC analysis, both MFI DSAmax (AUC 0.83; 3.75K had 92% sensitivity, 72% specificity) and DSAcum (AUC 0.85; 11.2K had 67% sensitivity, 92% specificity) were good predictors of AHR. Pretransplant DSA have a deleterious effect on kidney graft outcomes. Class, number and specially strength of DSA modulate that effect and should be considered in DSA+ pts management, such as the complementary behavior of MFI DSAmax and DSAcum as predictors of AHR.