Salvadori Maurizio, Bertoni Elisabetta
Maurizio Salvadori, Elisabetta Bertoni, Department of Renal Transplantation, Careggi University Hospital, 50139 Florence, Italy.
World J Transplant. 2016 Dec 24;6(4):632-645. doi: 10.5500/wjt.v6.i4.632.
The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials.
肾移植后肾病复发正成为肾移植后移植物丢失的主要原因之一。这主要涉及一些原发性疾病，如非典型溶血尿毒综合征（HUS）、膜增生性肾小球肾炎（MPGN），特别是现在称为C3肾小球病的MPGN。这两组肾脏疾病的特征都是补体替代途径的先天性（遗传）或后天性（自身抗体）改变。这些异常在移植后往往仍然存在，因为它们是先天性的，且受免疫抑制的影响较小。这一事实解释了这些疾病的高复发率。只要有可能，复发的早期诊断对于最佳治疗方法至关重要。因C3肾小球病或非典型HUS导致终末期肾病的患者，在移植时可能需要极其谨慎。不建议亲属活体供肾，因为同一家族成员可能受到相同基因突变的影响。为预防和治疗复发尝试了不同的治疗方法。最有前景的方法是补体抑制剂。依库珠单抗，一种抗C5转化酶的单克隆抗体，是最有前景的药物，尽管迄今为止尚不清楚治疗应持续多长时间以及最佳剂量是多少。这些情况导致了治疗成本高昂。已经描述了对依库珠单抗耐药的患者。他们可能会从C3转化酶抑制剂中获益，但这类药物目前是随机对照试验的对象。
