Genberg Helena, Kumlien Gunilla, Wennberg Lars, Tydén Gunnar
Department of Transplantation Surgery, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
Transfus Apher Sci. 2010 Oct;43(2):231-5. doi: 10.1016/j.transci.2010.07.016. Epub 2010 Jul 27.
As the demand for kidney transplantation is constantly growing methods to expand the donor pool have become increasingly important. ABO-incompatibility has hitherto been regarded as an absolute contraindication to living donor donation. However, as ABO-incompatibility has accounted for the majority of living donor exclusions, efforts have been made to overcome this immunologic barrier. Successful desensitization protocols thus far, have combined plasmapheresis for antibody removal with splenectomy to reduce the antibody producing B-cell pool, in addition to quadruple immunosuppression. Although good graft function has been achieved, the high risks involved have been deterrent. We have developed a protocol for ABO-incompatible kidney transplantation based on antigen-specific immunoadsorption and rituximab, in combination with standard maintenance immunosuppression (tacrolimus, mycophenolate mofetil and corticosteroids). We hypothesized that the anti-A/B antibodies could be effectively eliminated and good graft function achieved, without the complications of coagulopathy and transfusion reactions associated with plasmapheresis. Furthermore, we hypothesized that the substitution of splenectomy with a single dose of the anti-CD20 antibody rituximab would further reduce surgical risk as well as the risk of infectious complications. In 2001 the program for ABO-incompatible kidney transplantation was started at our center. To date 50 ABO-incompatible kidney transplantations have been performed according to the protocol based on antigen-specific immunoadsorption and rituximab. Safety and efficacy of the protocol has been evaluated in several studies, all showing that the antigen-specific immunoadsorption is well tolerated and without any serious side effects. Patient and graft survival as well as kidney function have been comparable to that of ABO-compatible living donor kidney transplantation and the incidence of antibody-mediated rejection 0%. We conclude that AB0-incompatible kidney transplantation using a protocol based on antigen-specific immunoadsorption and rituximab, in combination with triple immunosuppressive therapy is safe and effective. ABO-incompatibility following this protocol does not have a negative impact on graft function. ABO-incompatible kidney transplantation is equivalent to standard ABO-compatible living donor kidney transplantation.
随着肾移植需求的不断增长，扩大供体库的方法变得越来越重要。ABO血型不相容迄今一直被视为活体供体捐献的绝对禁忌证。然而，由于ABO血型不相容占活体供体排除的大多数，人们一直在努力克服这一免疫障碍。迄今为止，成功的脱敏方案除了四联免疫抑制外，还将用于去除抗体的血浆置换与脾切除术相结合，以减少产生抗体的B细胞库。尽管已实现良好的移植肾功能，但所涉及的高风险具有威慑力。我们基于抗原特异性免疫吸附和利妥昔单抗，结合标准维持免疫抑制（他克莫司、霉酚酸酯和皮质类固醇），制定了ABO血型不相容肾移植方案。我们假设抗A/B抗体能够被有效清除，并实现良好的移植肾功能且无血浆置换相关的凝血障碍和输血反应并发症。此外，我们假设用单剂量抗CD20抗体利妥昔单抗替代脾切除术将进一步降低手术风险以及感染并发症风险。2001年我们中心启动了ABO血型不相容肾移植项目。迄今为止，已根据基于抗原特异性免疫吸附和利妥昔单抗的方案进行了50例ABO血型不相容肾移植。该方案的安全性和有效性已在多项研究中得到评估，所有研究均表明抗原特异性免疫吸附耐受性良好且无任何严重副作用。患者和移植肾存活率以及肾功能与ABO血型相容的活体供肾移植相当，抗体介导的排斥反应发生率为0%。我们得出结论，采用基于抗原特异性免疫吸附和利妥昔单抗并联合三联免疫抑制治疗的方案进行ABO血型不相容肾移植是安全有效的。按照该方案的ABO血型不相容对移植肾功能没有负面影响。ABO血型不相容肾移植等同于标准的ABO血型相容活体供肾移植。
