Acute Antibody-Mediated Rejection in Living ABO-Incompatible Kidney Transplantation: Long-Term Impact and Risk Factors

Abstract

The impact of acute antibody-mediated rejection (AAMR) on the long-term outcome on ABOincompatible (ABOIOur results indicate that AAMR has a heavy impact on the long-term outcome and preoperative DSHA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOI kidney transplantation.

Alloantibodies Prevent the Induction of Transplantation Tolerance by Enhancing Alloreactive T Cell Priming

“…A consensus is emerging that donor-specific Abs (DSAs) are predictive of poor graft outcome (30,31), and the activation of complement downstream of DSA binding to graft endothelium comprises the currently accepted paradigm for the mechanistic basis of how DSA effects graft loss (32). The observations in this study challenge the limited scope of this paradigm and demonstrate the ability of alloantibodies to function as opsonins to facilitate CD40-CD154-independent T cell activation and the rejection of allogeneic heart and skin grafts.…”

Transplanting Against Histocompatibility Barriers

“…In a study by Shimmura et al pretransplant anti-A/anti-B titers were not found to correlate with graft survival in the patients with anti A/B IgG titers [29]. However, the presence of donor specific anti-HLA antibodies did appear to have a more significant association with poor allograft outcomes than antiblood group antibodies [28]. In another study, the authors found that the median anti-A/anti-B titer in those who had antibody mediated rejection was 16 (range 8-256).…”

“…Acute antibody mediated rejection (AMR) has also been shown to affect graft survival in ABOi kidney transplants. Toki [28] et al showed that the graft survival is much lower when patients have AMR compared to patients who do not experience AMR (5 year survival-84% vs. 95%). Presence of AMR also correlates with the development of transplant glomerulopathy at 1 year (64% vs. 3%).…”

“…However, the positive predictive value of a high anti-A/B titers for AMR was poor (33.3%) [30]. Other studies have found that the absence of mycophenolate mofetil in the conditioning regimens was also associated with an increased risk of rejection [2, [28][29][30].…”

The Impact of Donor Type and Quality on Renal Transplant Outcomes

“…Acute AMR occurred in up to 30% of transplant recipients resulting in early graft loss in 10% of recipients with refractory AMR . Although acute AMR may be treated successfully with further immunoabsorption or plasmapheresis, recipients who develop AMR have poorer graft survival (AMR and no AMR -graft survival of 84% and 100% at 3 years and 49% and 95% at 8 years) and a greater risk of developing transplant glomerulopathy, especially in recipients with concurrent pre-transplant donor specific antibodies (DSA) (Einecke, Sis et al 2009;Toki, Ishida et al 2009). Acute AMR is less common after 3 months post-transplant, presumably related to the development of accommodation, a phenomenon of persistent anti-donor antibody in the absence of allograft injury (Dehoux and Gianello 2009).…”