ABO-Incompatible Renal Transplantation Without Antibody Removal Using Conventional Immunosuppression Alone

Abstract

Masterson et al had shown that in their series of 20 patients with low blood group antibody titers (ABGAb) who underwent ABO-incompatible (ABOi) live donor renal transplantation with standard immunosuppression and without antibody removal had 100% patient and graft survival at the end of 36 months (1). We report two patients from our centers who received ABOi live donor renal transplantation with low-level ABGAb with standard immunosuppression and no antibody removal, but with opposite results.A 73-year-old female, blood group O, previous bone marrow transplantation with splenic radiation for leukemia, received a blood-group B kidney. Pretransplant anti-B IgG titer was 0 and IgM was 2 with low levels confirmed on several occasions pretransplant and immediately pretransplant. IgM titers were measured by direct agglutination, IgG titers by indirect agglutination with dithiothrietol, both using a gelcard method (Bio-Rad, Hemel Hempstead, UK). No donor HLA-specific antibodies were detected. Immunosuppression was basiliximab, tacrolimus, prednisolone, and mycophenolate. Posttransplant, the serum creatinine, was 65 umol/L on day 5. On the sixth day posttransplant, she was noted to have raised liver function tests. This was thought to be due to mycophenolate toxicity and hence mycophenolate was stopped. On day 8, her urine output had reduced significantly, creatinine had increased to 213, blood and urine cultures grew E. coli and anti-B titers were IgG 2 and IgM 8. She was started on anti-thymocyte globulin. The next day, the urine output reduced further and the anti-B titers were IgG 8 and IgM 64. A biopsy showed infarction of the kidney with acute antibody-mediated rejection (AMR) and she had transplant nephrectomy. The peak anti-B titers on day 13 were IgG 32 and IgM 2048.A 32-year-old female, blood group A, with renal failure due to diabetic nephropathy, received a kidney from her blood group AB mother. She had no anti-HLA donor-specific antibodies. The recipient's anti-B IgG titer was 1 and IgM was 8 with low levels confirmed immediately pretransplant. She received alemtuzumab induction and tacrolimus. After initial graft function, she was noted on day 3 to have red cell fragmentation with low platelets and raised LDH levels. She was thought to have microangiopathic hemolytic anemia (MAHA) and hence tacrolimus was stopped temporarily. On day 7, the serum creatinine rose further, the anti-B titers were IgG 8 and IgM 32, and HLA antibody screening was negative, biopsy showed thrombosis of the graft with AMR and the graft was removed the next day. Anti-B titers were IgG 32 and IgM 512 on day 8.In both these cases, the pretransplant blood group antibody levels were low, and there were no anti-HLA antibodies detected. We did not test for anti-angiotensin 1 receptor antibodies. Biopsy appearances confirmed acute AMR, and the rises in ABO antibody levels implicated these as the driver of graft failure. It can be speculated that an infective episode and drug toxicity or slight reduction in immunosuppression could potentia...

ABO-incompatible kidney transplantation as a renal replacement therapy—A single low-volume center experience in Japan

“…It might therefore become possible to simplify desensitization protocols in the future. However, patients with low anti-A/B antibody titers undergoing ABO-IKT without desensitization had acute antibody-mediated rejection, resulting in graft loss [34].…”

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

“…We thank Dr. Focosi et al and Dr. Krishan et al for their comments regarding the recent article describing ABOincompatible renal transplantation (ABOi) without antibody removal using conventional immunosuppression alone (1,2). In the manuscript, we highlighted the role of antiblood group antibody (ABGAb) titer as the major predictor of antibody-mediated rejection (AbMR) in ABOi.…”

ABO‐incompatible living kidney transplantation

“…Patients with an anti‐A/B titer of ≤1:16 did not have to undergo blood group antibody or B‐cell depletion 40 . However, acute graft loss resulting from AMR was reported in another study, which appeared to invalidate the correlation between high pretransplant anti‐A/B IgG and graft loss 40‐42 …”