ABO Incompatible Renal Transplantation: A Paradigm Ready for Broad Implementation

Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Transplantation (Impact Factor: 3.83). 05/2009; 87(8):1246-55. DOI: 10.1097/TP.0b013e31819f2024
Source: PubMed


The requirements for potent immunosuppression coupled with the formidable risk of irreversible antibody-mediated rejection (AMR) have thus far limited the expansion of ABO incompatible (ABOi) kidney transplantation. We present a retrospective review of our single-center experience with 60 consecutive ABOi kidney transplants and describe the evolution of our treatment protocol to one that consists only of a brief escalation in immunosuppression without long-term B-cell suppression from splenectomy or anti-CD20. The 1-, 3-, and 5-year graft survival rates for the cohort were 98.3%, 92.9%, and 88.7%, respectively, which is comparable with United Network for Organ Sharing data for compatible live donor transplants. No instances of hyperacute rejection were observed, and no grafts were lost secondary to AMR. In fact, fewer than 15% of the patients experienced a clinical episode of AMR, and rejections were mild. Elimination of B-cell ablative therapies did not result in an increased incidence of AMR. Excellent graft function persists with a current median creatinine clearance of 60 mL/min. The findings of this study and the relatively simple therapeutic regimen used should facilitate widespread application of ABOi kidney transplantation resulting in one of the most rapid escalations in access to organs in the modern era of kidney transplantation.

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    • "The risks and benefits associated with ABO non-identical transplant were explained to the patient and written consent was obtained from the patient . The protocol planned was similar to that of the John Hopkin's Hospital [1], wherein the patient, depending upon his antibody titer, would have successive one-volume PP on alternate days both preoperatively and post-operatively , along with immunosuppressions to lower the antibody (anti-B in this patient) titer to, or less than 16. The immunosuppressive agents that were being administered were intra-venous Immuno-Globulin (IVIG), Mycophenolate mofetil (an inhibitor of lymphocyte proliferation and activation) and Tacrolimus (which reduces IL-2 by T cells). "
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    ABSTRACT: The biggest hurdle in renal transplantation is the ABO blood group system. But recently ABO incompatible renal transplants have been performed using plasmapheresis (PP) as a part of the preconditioning protocol. In the present study, the objective of PP along with immunosuppression was to bring down the antibody titer of the patient to ⩽16 during the transplant and keep it low, around 32, until post-operative 4-14weeks. The patient (O Negative) had his mother (B Positive) as the ABO non-identical donor. The PP was performed with an apheresis equipment Com.Tec (Fresenius Kabi, Germany) to lower the anti-B antibody titer in the recipient. An Antihuman globulin (AHG) titer was performed for anti-B antibody following the departmental standard operating procedure. A total of 11 plasmapheresis procedures was performed preoperatively and four procedures were performed post-operatively to maintain the titer of the anti-B antibody at or below the desired level. The baseline anti-B antibody titer in the recipient was 512. The baseline titer came down to 8 after the end of the 11th procedure. Post-operatively we performed four plasmapheresis procedures to keep the titer at 32. During the post-operative follow up the titer has been maintained at 32 and the serum creatinine level has been maintained at approximately 1.0mg/dl and other parameters relevant to graft function were within normal limits. Our case could be the first reported case from India in which we used a plasmapheresis procedure as a part of preconditioning protocol instead of using an immunoadsorption column. Furthermore, it could be one of the few ABOiRTx cases, which has been performed at an isoagglutinin titer of 512 using plasma exchange as part of a preconditioning regime.
    Full-text · Article · Jul 2013 · Transfusion and Apheresis Science
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    • "Montgomery et al.[10] published their experience of 60 ABOi transplants and of these patients 32 patients had received splenectomy or rituximab or both, whereas 28 patients had no splenectomy and no rituximab. The outcomes of these two subgroups were comparable. "
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    ABSTRACT: In India, patients without a compatible blood group donor are usually excluded from renal transplantation. For young patients, it is a difficult therapeutic choice to stay on long-term dialysis. We describe the case of a 19-year-old male patient who had blood group O +ve and had no compatible donor in the family. His mother was B +ve and was willing to donate. The patient had an initial anti-B antibody titer of 1:512 and underwent antibody depletion with plasmapheresis (11 sessions) and intravenous immunoglobulin (IVIG) 100 mg/kg after every plasmapheresis. He also received rituximab 500 mg for 3 days prior to transplant and was induced with basiliximab. At the time of transplant, his anti-B titers were <1:8. Post-operatively, he required four sessions of plasmapheresis and IVIG as his titers rebounded to 1:64. The titers then spontaneously subsided to <1:16 and have stayed at the same level for 6 months post-transplant. The patient continues to have normal renal function with a creatinine of 1.4 mg/dl% and has had no episodes of rejection.
    Full-text · Article · May 2013 · Indian Journal of Nephrology
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    • "This fact has extremely important implications for therapeutic strategy in ABOincompatible organ transplantation. If posttransplant antibody production can be suppressed, then acute AMR can be avoided; i.e., the most important treatment step for ensuring a successful graft outcome is pretransplant suppression of host B cell immunity (desensitization therapy) [7] [15] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]. Fig. 1. "
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    ABSTRACT: Owing to the shortage of deceased donors in Japan, since 1989, we have performed ABO-incompatible kidney transplantation (ABO-IKTx) to expand the indication for living donor kidney transplantation. During the past two decades, about 2000 ABO-IKTxs were performed. Since 2001 the success rate for these kidney transplants has reached 96% for 1-year, 91% for 5-year and 83% for 9-year graft survival, similar to outcomes of ABO-compatible kidney transplantation (ABO-CKTx). This dramatic improvement in results means that ABO-IKTx has become accepted as a therapeutic alternative for end-stage renal failure. Today ABO-IKTx accounts for approximately 30% of all living donor kidney transplantations performed in Japan. We have been making a lot of efforts to elucidate the mechanism of acute antibody-mediated rejection in ABOI-KTx in order to overcome the ABO barrier and to improve the outcome. From careful and precise clinical observations, proteomic analysis of ABO histo-blood group antigens in graft endothelial cells and deep insight into immunology and biology, we have reached the hypothesis that the structural difference of ABO histo-blood group antigens and de novo corresponding antibody production would be the key and keyhole of the development of acute AMR in ABOI-KTx. Preoperative desensitization therapy would be the best solution for the suppression of acute AMR and graft loss, which is now widespread and improves the outcome.
    Preview · Article · Aug 2012 · Transplantation reviews (Orlando, Fla.)
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