ABO-Incompatible Kidney Transplantation

Abstract

ABO-incompatible (ABOi) kidney transplantation has long been considered a contraindication to successful kidney transplantation. During the last 25 years, increasing organ shortage enforced the development of strategies to overcome the ABO antibody barrier. In the meantime, ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantations. Desensitization is usually achieved by apheresis and B cell-depleting therapies that are accompanied by powerful immunosuppression. Anti-A/B antibodies are aimed to be below a certain threshold at the time of ABOi kidney transplantation and during the first 2 weeks after surgery. Thereafter, even a rebound of anti-A/B antibodies does not appear to harm the kidney transplant, a phenomenon that is called accommodation, but is poorly understood. There is still concern, however, that infectious complications such as viral disease, Pneumocystis jirovecii pneumonia, and severe urinary tract infections are increased after ABOi transplantations. Recent data from the Collaborative Transplant Study show that during the first year after kidney transplantation, one additional patient death from an infectious complication occurs in 100 ABOi kidney transplant recipients. Herein, we review the recent evidence on ABOi kidney transplantation with a focus on desensitization strategies and respective outcomes.

T cell reconstitution after lymphocyte depletion features a different pattern of inhibitory receptor expression in ABO- versus HLA-incompatible kidney transplant recipients

“…However, these carbohydrates are often expressed as glycoproteins [6,28]: they can possibly induce T cell-dependent immunity. B cell isoagglutinins could occur in early childhood, probably induced by the cell membrane polysaccharides of commensal bacteria [7]. Natural isoagglutinins are mainly of the IgM class, but they also consist of IgG and IgA classes, and the levels and distribution patterns of these immunoglobulin types and subclasses vary with individuals and blood groups [7].…”

“…B cell isoagglutinins could occur in early childhood, probably induced by the cell membrane polysaccharides of commensal bacteria [7]. Natural isoagglutinins are mainly of the IgM class, but they also consist of IgG and IgA classes, and the levels and distribution patterns of these immunoglobulin types and subclasses vary with individuals and blood groups [7]. Moreover, the role of isoagglutinin types in rejection remains to be elucidated [7], and the pathogenic potential is also dependent on the blood group CD5 + B-1 or B-2 cells [6].…”

“…Natural isoagglutinins are mainly of the IgM class, but they also consist of IgG and IgA classes, and the levels and distribution patterns of these immunoglobulin types and subclasses vary with individuals and blood groups [7]. Moreover, the role of isoagglutinin types in rejection remains to be elucidated [7], and the pathogenic potential is also dependent on the blood group CD5 + B-1 or B-2 cells [6]. In ABOi patients there was a progressive reconstitution of a normal IR phenotype, akin to that found in HD.…”

“…However, transplantation across the ABO blood group barrier leads to similar outcomes compared with ABO-compatible KT [3][4][5]. Nonetheless, the treatment used in both incompatible KTs is similar, including (i) the use of multiple maintenance immunosuppressive therapies, such as calcineurin inhibitors (CNIs), anti-metabolites or mammalian target of rapamycin (m-TOR) inhibitors, (ii) the pretransplant elimination of circulating antibodies by apheresis sessions and (iii) the depletion of B cells with anti-CD20 monoclonal antibody, associated with a T cell targeting agent, resulting in almost complete elimination of circulating lymphocytes, including T, B and natural killer (NK) cells [6,7]. Following this conditioning, lymphocytes populations will be progressively reconstituted in the periphery.…”

Accommodation and related conditions in vascularized composite allografts

“…In organ transplants, accommodation is typically recognized when the presence of DSA in blood was not paralleled by rejection. Although accommodation is readily detected in ABO-incompatible organ transplants (59) it is more difficult to appreciate in ABO-compatible transplants (44, 46). Accommodation can be difficult to detect because normal organs have the capacity to absorb large amounts of antibody, depleting much or all DSA from blood.…”