ABO Incompatible Renal Transplantation Without Antibody Removal Using Conventional Immunosuppression Alone

Abstract

ABO incompatible living donor renal transplantation (ABOi) can achieve outcomes comparable to ABO compatible transplantation (ABOc). However, with the exception of blood group A2 kidneys transplanted into recipients with low titer anti‐A antibody, regimens generally include antibody removal, intensified immunosuppression and splenectomy or rituximab. We now report a series of 20 successful renal transplants across a range of blood group incompatibilities using conventional immunosuppression alone in recipients with low baseline anti‐blood group antibody (ABGAb) titers. Incompatibilities were A1 to O (3), A1 to B (2), A2 to O (2), AB to A (2), AB to B (1), B to A1 (9), B to O (1); titers 1:1 to 1:16 by Ortho. At 36 months, patient and graft survival are 100%. Antibody‐mediated rejection (AbMR) occurred in one patient with thrombophilia and low level donor‐specific anti‐HLA antibody. Four patients experienced cellular rejection (two subclinical), which responded to oral prednisolone. This series demonstrates that selected patients with low titer ABGAb can undergo ABOi with standard immunosuppression alone, suggesting baseline titer as a reliable predictor of AbMR. This reduces morbidity and cost of ABOi for patients with low titer ABGAb and increases the possibility of ABOi from deceased donors.

ABOi With Conventional Immunosuppression Alone–Antiblood Group Antibody Isn’t the Only Contributor to Antibody-Mediated Rejection and/or Thrombotic Microangiopathy

“…In the manuscript, we highlighted the role of antiblood group antibody (ABGAb) titer as the major predictor of antibody-mediated rejection (AbMR) in ABOi. The occurrence of AbMR in only 1 of 20 low-titer patients in conjunction with the series of 10 low-titer patients from Cambridge without AbMR (3), and multiple reports of AbMR occurring primarily in patients with moderate to high baseline ABGAb strongly suggest that titer is the prime (though not sole) predictor of AbMR.…”

“…Focosi highlights the recognized idiosyncrasies of measuring ABGAb, reinforcing the need for center specific thresholds in considering the need for antibody removal, and deciding the number of treatments required in the perioperative period (3,4). As stated in the study design, we measure ABGAb by three methodologies using both standard and donor-specific cells and donor-specific cells.…”

“…other causes of thrombotic microangiopathy [TMA] with associated C4d staining) (7). The correspondence from Dr. Krishnan draws attention to phenomena we and others have noted previously with regards to additional factors that may contribute to, produce, or moderate the pathology seen with AbMR; this includes use of lymphocyte-depleting antibodies (6,8,9), particularly in the setting of ABOi (3,4).…”

“…With regards to the expression and pathology of AbMR, the potential for important interactions between pathways governing humoral immunity, coagulation, complement, complement regulatory proteins and other constitutive endothelial protective mechanisms has been noted (3,19). Phenotypic variations/abnormalities in these pathways may alter the pathogenicity of alloantibody, potentially lowering the threshold that triggers AbMR as described in a patient with a factor H mutation (10).…”

“…Use of T lymphocyte-depleting antibodies has been associated with deposition of complement (14), production of DSAb (9), and development of AbMR (9,15). Given the profound changes in immunobiology that occur following administration of either thymoglobulin or alemtuzemab, it is possible they may interfere with subsets of lymphocytes controlling alloantibody production (16), and/or the constitutive mechanisms governing the phenomenon of accommodation (3,4).…”