Histopathologic Features of Antibody Mediated Rejection: The Banff Classification and Beyond

Antibody mediated rejection (ABMR) in the kidney can show a wide range of clinical presentations and histopathologic patterns. The Banff 2019 classification currently recognizes four diagnostic categories: 1. Active ABMR, 2. Chronic active ABMR, 3. Chronic (inactive) ABMR, and 4. C4d staining without evidence of rejection. This categorization is limited in that it does not adequately represent the spectrum of antibody associated injury in allograft, it is based on biopsy findings without incorporating clinical features (e.g., time post-transplant, de novo versus preformed DSA, protocol versus indication biopsy, complement inhibitor drugs), the scoring is not adequately reproducible, and the terminology is confusing. These limitations are particularly relevant in patients undergoing desensitization or positive crossmatch kidney transplantation. In this article, I discuss Banff criteria for these ABMR categories, with a focus on patients with pre-transplant DSA, and offer a framework for considering the continuum of allograft injury associated with donor specific antibody in these patients.

Positive Crossmatch Kidney Transplantation: State of the Art and Future Perspectives

The organ shortage for kidney transplantation remains a challenging issue worldwide. Incompatibility between donor-recipient pairs, commonly occurring among transplant candidates who were sensitized from prior antigen exposure, serves as a significant barrier to kidney transplantation. In efforts to overcome this obstacle, living and deceased donor kidney transplantation across human leukocyte antigen barriers following desensitization has been pursued via positive crossmatch transplantation. The goal of desensitization therapy is to remove or denigrate donor-specific alloantibodies prior to transplantation in order to permit transplantation across the human leukocyte antigen barrier and prevent rejection. Various desensitization regimens have been utilized, including the use of plasmapheresis, intravenous immunoglobulin, and or immunoadsorption. Although long-term allograft outcomes for positive crossmatch kidney transplantation following desensitization therapy have been shown to be inferior to compatible transplantation, particularly with increasing strength of the crossmatch, there is an established survival benefit for positive crossmatch transplant recipients compared with remaining on the transplant waitlist. However, positive crossmatch transplantation may confer higher risks of infection and malignancy. Despite the fact that some of these heightened risks, positive crossmatch transplantation has also been demonstrated to have cost-savings compared with remaining on dialysis and may, therefore, be a cost-effective treatment option for sensitized patients who would face long waiting times and may never be able to achieve compatible transplantation. This review highlights both the risks and benefits of positive crossmatch transplantation and its role in the broader field of kidney transplantation.

Transplant outcomes in positive complement-dependent cytotoxicity- versus flow cytometry-crossmatch kidney transplant recipients after successful desensitization: a retrospective study

Background Despite the obvious survival benefit compared to that among waitlist patients, outcomes of positive crossmatch kidney transplantation (KT) are generally inferior to those of human leukocyte antigen (HLA)-compatible KT. This study aimed to compare the outcomes of positive complement-dependent cytotoxicity (CDC) crossmatch (CDC + FC+) and positive flow cytometric crossmatch (CDC-FC+) with those of HLA-compatible KT (CDC-FC-) after successful desensitization. Methods We retrospectively analyzed 330 eligible patients who underwent KTs between June 2011 and August 2017: CDC-FC- (n = 274), CDC-FC+ (n = 39), and CDC + FC+ (n = 17). Desensitization protocol targeting donor-specific antibody (DSA) involved plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab with/without bortezomib for positive-crossmatch KT. Results Death-censored graft survival and patient survival were not different among the three groups. The median estimated glomerular filtration rate was significantly lower in the CDC + FC+ group than in the compatible group at 6 months (P < 0.001) and 2 years (P = 0.020). Biopsy-proven rejection within 1 year of CDC-FC-, CDC-FC+, and CDC + FC+ were 15.3, 28.2, and 47.0%, respectively. Urinary tract infections (P < 0.001), Pneumocystis jirovecii pneumonia (P < 0.001), and cytomegalovirus viremia (P < 0.001) were more frequent in CDC-FC+ and CDC + FC+ than in CDC-FC-. Conclusions This study showed that similar graft and patient survival was achieved in CDC-FC+ and CDC + FC+ KT compared with CDC-FC- through DSA-targeted desensitization despite the higher incidence of rejection and infection than that in compatible KT.

Effect of simultaneous presence of anti-blood group A/B and -HLA antibodies on clinical outcomes in kidney transplantation across positive crossmatch: a nationwide cohort study

ABO-incompatible (ABOi) and positive crossmatch (XM) kidney transplantation (KT) have been considered immunologically challenging. The present study analyzed the clinical outcomes in XM positive KT based on ABO incompatibility. We used data from the Korea Organ Transplantation Registry, a nationwide database, and a single-center registry. A total of 263 patients with positive XM were divided into an ABO compatible (ABOc) & XM positive (ABOc/XM+, n = 176) group and an ABOi & XM positive (ABOi/XM+, n = 87) group. The overall rejection rate one year after KT was significantly higher in the ABOi/XM+ group than in the ABOc/XM+ group (P < 0.01). A total of four mortalities occurred, all in the ABOi/XM+ patients (P < 0.01). There were no differences in surgical complications or the occurrence of infection-related complications, including BK virus nephropathy. Multivariate analysis indicated that female vs. male (odds ratio (OR), 2.27; P = 0.03), DSA class I (MFI/1000) (OR, 1.10; P = 0.03), DSA class II (MFI/1000) (OR, 1.10; P < 0.01), and ABOi & XM+ status (OR, 2.38; P < 0.01) were significant risk factors for acute rejection during the year after transplantation. Overall graft survival was inferior in ABOi/XM+ patients than in ABOc/XM+ patients (P = 0.02). ABO incompatibility in XM-positive KT patients was found to be a significant risk factor for the development of rejection within one year after transplantation as well as for long-term graft survival. The anti-blood group A, B and anti-HLA antibodies may show synergistic activity.

The Challenge of Transfusion of Patients Infected with HIV/AIDS

The transfusional support of human immunodeficiency virus-infected patients is a challenge both for the clinical physician and for the blood services, either because of the immunohematological problems or the microbiological/thrombotic risk associated. The immunohematological risk caused by positive crossmatch is resolved by autologous adsorption; if the patient was recently transfused, the adsorption will be homologous. The thrombotic risk (due to hypercoagulable state) is resolved by pretransfusion heparin administration and leukoreduction only in autoimmune hemolytic anemia cases; and the presumed microbiological risk is similar to HIV-negative patients.