ABO Incompatible Renal Transplantation: A Paradigm Ready for Broad Implementation
ABSTRACT 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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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.Transfusion and Apheresis Science 07/2013; 49(1). DOI:10.1016/j.transci.2012.09.010 · 1.07 Impact Factor
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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.Transplantation reviews (Orlando, Fla.) 08/2012; 27(1). DOI:10.1016/j.trre.2012.07.003 · 2.68 Impact Factor
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ABSTRACT: Desensitization strategies for ABO-incompatible renal transplants with plasma exchange (PE) or specific immunoadsorption (IA) decrease immunoglobulin levels. After recent measles outbreak and decreasing vaccination rates, we studied the impact of apheresis on anti-measles antibodies. Anti-measles antibodies were measured before desensitization, before transplantation and during followup in 12 patients with ABO incompatibility (2x PE only, 8x IA only, and 2x IA and PE) and 3 patients with donor-specific HLA antibodies (all PE). Patients received rituximab, IVIG, and standard immunosuppressive therapy. All patients had detectable anti-measles antibodies before desensitization (mean 3238 mU/l, range 560-8100). After 3-6 PE sessions, titers decreased significantly to 1710 mU/l (P < 0.05), in one patient to nondetectable values, while IA only maintained protective titers. After a median followup of 64 days, anti-measles antibodies returned to baseline in all patients. Immunity against measles was temporarily reduced by apheresis but remained detectable in most patients at time of transplantation. Desensitization maintains long-term protective immunity against measles.Journal of Transplantation 12/2011; 2011:869065. DOI:10.1155/2011/869065