INTRODUCTION: The immoderate donor shortage and sophisticated desensitization protocols resulted in the explosive increase and great success of the ABO blood type incompatible kidney transplantation [ABOiKTX] in Japan. The standard desensitization protocols comprising tacrolimus [TAC], mycophenolate mofetil [MMF], corticosteroid [CS] and rituximab [RIT] with some sessions of plasmapheresis [PP] have been used. However, the effect of corticosteroid against B-1a cells that play an important role in producing anti-ABO blood type antibody is skeptical. In contrast, everolimus [EVR] can suppress Bcell proliferation totally [Ide and Ohdan et al.]. In order to ensure ABOiKTX, as reported in the preliminary presentation of ATC2014, we have used EVR together with TAC and MMF instead of CS and discuss the outcome with additional cases.

METHODS: 87 consecutive patients with end-stage renal disease who attempted ABOiKTX from living donors were surveyed. According to the desensitization protocols, the patients were divided into two groups, namely Control Group [n=60]; TAC/MMF/CS/RIT/PP and EVR Group [n=27]; TAC/MMF/EVR/RIT/PP. EVR was initiated from the beginning of desensitization with a 1.5mg/day for loading dose and adjusted aiming at the range 3-6 ng/mL. The duration of desensitization depended on anti-ABO IgM or IgG titer, such as from D-28 for 128x or higher, from D-14 for 64x, from D-7 for 32x or lower. RIT was administerd 100-200mg/body according to the titer. The most patients received 2 to 4 sessions of PP immediately before ABOiKTx. We compared the change of anti-ABO IgG titer between the initial and just prior to PP and analyzed the outcome of kidney transplantation in the two groups.

RESULTS: The patients' characteristics were comparable except for the dialysis period and the follow-up period. The strength of initial anti-ABO IgG titer was also comparable. Interestingly, the spontaneous decreases of anti-ABO IgG titer before PP were more frequently seen in EVR Group [13 out of 27 patients] than in Control Group [11out of 60] [p=0.0099]. Incidence of early graft loss was only seen in Control Group [3 out of 60]. In EVR group, all kidney grafts are well functioning and patients are alive without any severe events.

CONCLUSION: The spontaneous decline of anti-ABO titer just before PP would be the synergistic effect of EVR on TAC and MMF. EVR holds the great promise of the alternative to gold standard CS in desensitization protocols for ABOiKTX.

CITATION INFORMATION: Wada Y, Fukuzawa N, Harada H. Everolimus Decline Anti-ABO Blood Type Antibody Titer in Desensitization for ABO Incompatible Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).

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