Evaluation of blood group antibodies in ABO-incompatible living-donor kidney transplantation.

To assess changes in anti-blood type antibody titers and postoperative outcomes (graft survival and rejection rates) at our center with the use of the immunosuppressant, rituximab, in ABO-incompatible kidney transplants from living donors. Confirming anti-donor blood group antibodies is important for avoiding humoral rejection in ABO-incompatible kidney transplants. Splenectomy has been carried out in our hospital according to Alexandre's policy in order to suppress the production of anti-donor blood group antibodies. However, splenectomy has recently been avoided due to the administration of the immunosuppressant rituximab, which gives satisfactory outcomes. Thus, pre- and postoperative anti-donor blood group antibodies were measured, and the outcomes achieved with rituximab were examined. A total of 134 cases of ABO-incompatible kidney transplants were carried out at Toho University Omori Medical Center between March 1989 and February 2013. These cases were classified as follows: azathioprine group (n = 62 patients); mycophenolate mofetil group (n = 33 patients); rituximab group (n = 39 patients). The anti-donor blood group antibodies levels (immunoglobulin G and immunoglobulin M) were measured in all groups before antibody removal, immediately before surgery, and 1, 2, 4 weeks and 3 months after surgery, and then compared. Rates of antibody-mediated rejection, including hyperacute rejection, in the azathioprine, mycophenolate mofetil, and rituximab groups were 32.2%, 18.1% and 7.6%, respectively. Graft survival rates were higher in the mycophenolate mofetil and rituximab groups than in the azathioprine group, but were lower in patients with higher preoperative antibody titers (≥128-fold higher immunoglobulin G) than in those with lower titers (<128-fold higher immunoglobulin G). In addition, postoperative anti-blood type antibody titers were significantly suppressed in the rituximab group. Administration of rituximab results in better antibody control than previous protocols including splenectomy, even in the postoperative period during which humoral rejection often occurs. This protocol eliminates the physical invasiveness of pre-transplant splenectomy, and is expected to provide better outcomes in chronic renal failure patients who undergo kidney transplants.

Sugiyama K ，Hyodo Y ，Aikawa A 《-》

Pinpoint targeted immunosuppression: anti-CD20/MMF desensitization with anti-CD25 in successful ABO-incompatible kidney transplantation without splenectomy.

Saito K ，Nakagawa Y ，Suwa M ，Kumagai N ，Tanikawa T ，Nishiyama T ，Ueno M ，Gejyo F ，Nishi S ，Takahashi K ... -  《xenotransplantation》

Long-term desensitization for ABO-incompatible living related kidney transplantation recipients with high refractory and rebound anti-blood type antibody: case report.

Nishimura H ，Yamada Y ，Hisano S ，Mitsuke A ，Tatarano S ，Gotanda T ，Hayami H ，Nakagawa M ，Enokida H ... -  《-》

The efficacy and safety of high-dose mizoribine in ABO-incompatible kidney transplantation using anti-CD20 and anti-CD25 antibody without splenectomy treatment.

Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but it shows less potent immunosuppressive effects at doses up to 3 mg/kg/d. In this study, we investigated whether high-dose MZR (6 mg/kg/d) was effective for ABO-incompatible (ABO-i) living donor kidney transplantation (LKT) using treatment with anti-CD25 and anti-CD20 monoclonal antibodies without splenectomy. Since 2007, we encountered 24 cases of ABO-i LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. The pretransplant immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF), prednisolone, a calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LKT up to several times according to the antibody titer. The posttransplant regimen consisted of high-dose mizoribine (6 mg/kg/d) instead of MMF (MZR group, n = 12). The 1-year graft survival rates for the MZR and MMF groups were both 100%. The rejection rate in the MZR group (eight %) was not significantly higher than that in the MMF group (seventeen %) Serum creatinine level was not significantly different between the two groups. In the MZR group 6 (50%) patients developed CMV antigenemia-positivity versus 11 (92%) in the MMF group (P < .05). The number of patients who developed CMV disease was 0 in the MZR group and 1 (8%) in the MMF group. The number of patients treated with ganciclovir was 0% and 8%, respectively (not significant). We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy.

Yoshimura N ，Ushigome H ，Matsuyama M ，Nobori S ，Suzuki T ，Sakai K ，Okajima H ，Okamoto M ... -  《-》

Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation.

Ashimine S ，Watarai Y ，Yamamoto T ，Hiramitsu T ，Tsujita M ，Nanmoku K ，Goto N ，Takeda A ，Katayama A ，Uchida K ，Kobayashi T ... -  《-》