Reducing Donor-specific Antibody During Acute Rejection Diminishes Long-term Renal Allograft Loss: Comparison of Early and Late Rejection

Abstract

Background. Reduction in donor-specific antibody (DSA) has been associated with improved renal allograft survival after antibody-mediated rejection (AMR). These observations have not been separately analyzed for early and late AMR and mixed acute rejection (MAR). The purpose of this study was to evaluate long-term responses to proteasome inhibitor–based therapy for 4 rejection phenotypes and to determine factors that predict allograft survival. Methods. Retrospective cohort study evaluating renal transplant recipients with first AMR episodes treated with proteasome inhibitor–based therapy from January 2005 to July 2015. Results. A total of 108 patients were included in the analysis. Immunodominant DSA reduction at 14 days differed significantly (early AMR 79.6%, early MAR 54.7%, late AMR 23.4%, late MAR 21.1%, P < 0.001). Death-censored graft survival (DCGS) differed at 3 years postrejection (early AMR 88.3% versus early MAR 77.8% versus late AMR 56.7% versus late MAR 54.9%, P = 0.02). Multivariate analysis revealed that immunodominant DSA reduction > 50% at 14 days was associated with improved DCGS (odds ratio, 0.12, 95% CI, 0.02-0.52, P = 0.01). Conclusions. In summary, significant differences exist across rejection phenotypes with respect to histological and DSA responses. The data suggest that DSA reduction may be associated with improved DCGS in both early and late AMR.

Differential Treatment Effects for Renal Transplant Recipients With DSA-Positive or DSA-Negative Antibody-Mediated Rejection

“…We also found that the timepoint of ABMR diagnosis is a crucial factor determining allograft outcome. Our observation is concordant with those of others showing that the late appearance of ABMR after transplant is a significant risk factor for rapid allograft loss (23,24).…”

Dynamic Behaviour of Donor Specific Antibodies in the Early Period Following HLA Incompatible Kidney Transplantation

“…In some cases, we observed no sustained fall in MFI values over a course of DFPP, and in others, we saw spontaneously MFI falls without DFPP use. A recent study ( 22 ) also showed that declining DSA levels following AMR associated with the good longer-term outcome, but the two cohorts are not directly comparable and with different approaches to AMR treatment, so it is unclear whether it is the treatment itself as opposed to the AMR process (and its successful resolution) that determines the outcome.…”

“…The presence of DSA post-transplantation was associated with an increased likelihood of AMR ( 17 – 19 ) and graft failure ( 12 , 20 , 21 ). Recent studies ( 22 , 23 ) suggest AMR may not always be associated with poor middle- or long-term graft failure (GF).…”

Defining Clinically Pathogenic HLA-Specific Antibodies - Granular Details in Characteristics in Pre and Early Time Following HLA-Antibody Incompatible Kidney Transplantation

“…All these studies have shown that understanding the role of HLA antibodies in graft outcome is more complex than previously thought, with a series of relatively weak clinical associations, and the understandable, but erroneous, concentration on AAMR as a surrogate for adverse clinical outcome. Some studies have suggested the long-term outcome following early episode of AAMR is not always detrimental [85,86] and thus studies relating characteristics with graft survival are important as studies using AAMR as an endpoint may be misleading. Hopefully, specific immunological assays will predict and explain the key immunological pathologies in transplantation.…”