Donauer Johannes, Wilpert Jochen, Geyer Marcel, Schwertfeger Eckhard, Kirste Günter, Drognitz Oliver, Walz Gerd, Pisarski Przemyslaw
Department of Nephrology, University Hospital Freiburg, Freiburg, Germany.
Xenotransplantation. 2006 Mar;13(2):108-10. doi: 10.1111/j.1399-3089.2006.00293.x.
For years ABO-incompatible kidney transplantations were preferentially performed in Japanese centers. In order to overcome the increased risk of humoral rejections, patients were treated with multiple sessions of plasmapheresis, intensified immunosuppressive therapy and splenectomy before transplantation. Despite good long-term results regarding patient and organ survival rates, increased morbidity during the early post-transplant period prevented a broad application of this method. Recently, a new protocol including the anti-CD20-antibody (Ab) rituximab and blood group-specific immunoadsorption instead of splenectomy and plasmapheresis was published with excellent short-term results.
From April 2004 to September 2005, 11 patients were prepared for ABO-incompatible transplantation. All patients received 375 mg/m2 rituximab intravenous 3 to 4 weeks before transplantation. Immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and prednisone and was started at least 7 days before transplantation. Intravenous immunoglobulins (0.5 g/kg) were administered the day before transplantation. Immunoglobulin G (IgG)-anti-A or -B Ab titers before starting immunoadsorption treatment ranged between 1 : 4 and 1 : 1024. Immunoadsorption treatment was started in parallel with immunosuppressive medication and was continued until the anti-A or anti -B Ab titers (IgG and IgM) were lowered to the aimed pre-transplant threshold of <1 : 8. During the early postoperative period, additional immunoadsorption treatments were performed, if the titers increased again above 1 : 8 (days 0 to 7) or 1 : 16 (days 8 to 14), respectively.
Transplantation could be conducted in eight of 11 patients (two females, six males, mean recipient age 52+/-11 yr). The mean follow-up was 7.0 months (range 4 to 17). The blood group constellation was A1 to 0 in four cases, A2 to 0 in two cases, B to A in one case, and A1 to B in another case, respectively. On average, each patient received seven immunoadsorption treatments. All transplants showed primary function and no humoral rejections occurred. Three of our 11 patients showed rapid increases of isoagglutinin titers after each immunoadsorption treatment and thus could not be transplanted. One patient died 4 months after transplantation with a functioning graft due to sepsis secondary to pseudomembranous enterocolitis. The mean creatinine value of the remaining seven patients now is 1.6 mg/dl.
The use of antigen-specific immunoadsorption and an immunosuppressive regimen consisting of a conventional triple immunosuppressive therapy has shown excellent short-term results. The immunoadsorption treatment using antigen-specific columns is highly effective and even patients with high isoagglutinin titers can be transplanted. This protocol is an option for end-stage renal disease patients who have no blood group-compatible donor.
多年来，ABO血型不相容的肾移植在日本的移植中心较为常用。为了降低体液排斥反应增加的风险，患者在移植前需接受多次血浆置换、强化免疫抑制治疗和脾切除术。尽管在患者和器官存活率方面有良好的长期效果，但移植后早期发病率的增加阻碍了该方法的广泛应用。最近，一种新的方案被公布，该方案包括使用抗CD20抗体利妥昔单抗和血型特异性免疫吸附，取代了脾切除术和血浆置换，短期效果良好。
2004年4月至2005年9月，11例患者准备接受ABO血型不相容移植。所有患者在移植前3至4周静脉注射375mg/m²利妥昔单抗。免疫抑制治疗包括他克莫司、霉酚酸酯和泼尼松，至少在移植前7天开始使用。移植前一天给予静脉注射免疫球蛋白（0.5g/kg）。开始免疫吸附治疗前，免疫球蛋白G（IgG）抗A或抗B抗体滴度在1:4至1:1024之间。免疫吸附治疗与免疫抑制药物同时开始，持续进行直至抗A或抗B抗体滴度（IgG和IgM）降至移植前目标阈值<1:8。术后早期，如果抗体滴度分别再次升高至>1:8（第0至7天）或>1:16（第8至14天），则进行额外的免疫吸附治疗。
11例患者中有8例（2例女性，6例男性，平均受者年龄52±11岁）成功进行了移植。平均随访时间为7.0个月（范围4至17个月）。血型组合分别为4例A1至O、2例A2至O、1例B至A和1例A1至B。平均每位患者接受了7次免疫吸附治疗。所有移植均显示原发性功能，未发生体液排斥反应。11例患者中有3例在每次免疫吸附治疗后同种凝集素滴度迅速升高，因此无法进行移植。1例患者在移植后4个月因假膜性小肠结肠炎继发败血症死亡，移植肾仍有功能。其余7例患者目前的平均肌酐值为1.6mg/dl。
使用抗原特异性免疫吸附和由传统三联免疫抑制治疗组成的免疫抑制方案已显示出良好的短期效果。使用抗原特异性柱的免疫吸附治疗非常有效，即使是同种凝集素滴度高的患者也可以进行移植。该方案是终末期肾病患者没有血型相容供体时的一种选择。
