Podocin-related mechanisms in posttransplantation recurrence of focal segmental glomerulsclerosis
Podocin-related mechanisms in posttransplantation recurrence of focal segmental glomerulsclerosis
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DOI：
10.1016/j.transproceed.2006.10.004
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发表时间：
2006-12-01
影响因子：
0.9
通讯作者：
Ghiggeri, G. M.
中科院分区：
文献类型：
--
作者：
Caridi, G.;Dagnino, M.;Ghiggeri, G. M.
局灶节段性肾小球硬化（FSGS）移植术后复发是人类病理学中最令人不安的事件之一，具有重要的社会和心理后果。它通常发生在30%至50%的受原发性疾病影响的患者中，大多数病例在移植后1个月内突然发作。预测复发病例和早期血浆置换治疗是治疗的主要目标。虽然移植后复发的机制仍不清楚，但已提出是多因素的起源，其中血浆因素决定裂膈蛋白质（如nephrin和podocin）的脱落，并伴有肾小球超滤单位的结构改变。由于杂合突变引起的podocin再合成低和/或单倍体不足应代表蛋白尿的显著易感因素。在这篇综述中，podocin在移植后复发中的作用将被评估，重点是蛋白质的再合成可能是肾滤过器稳定正常化的关键步骤。最近对podocin启动子顺式和反式作用元件的表征以及表征低和高podocin生产者单倍型的可能性提供了评估供体肾中podocin再合成能力的机会。对最初携带纯合和/或杂合NPHS 2突变的患者移植后FSGS复发的文献进行回顾，支持原发性疾病的多因素起源的一般想法，该想法可以扩展到移植后复发的发病机制。
Posttransplantation recurrence of focal segmental glomerulosclerosis (FSGS) is one of the most disarming events in human pathology with important social and psychological consequences. It usually occurs in 30% to 50% of patients affected by the primary form of the disease with an abrupt onset in the majority of cases occurring within I month of the transplantation. Prediction of recurrent cases and early therapy with plasmapheresis are the main goals of the therapy. Although the mechanism of posttransplantation recurrence is still obscure, it has been proposed to be of a multifactorial origin, in which plasma factors determine the shedding of proteins of the slit-diaphragm, such as nephrin and podocin, with structural alterations of the ultra-filtering unit of the glomerulus. Low resynthesis of podocin and/or haplo-insufficiency due to heterozygous mutations should represent significant predisposing factors to proteinuria. In this review, the role of podocin in posttransplantation recurrence will be evaluated focusing on the possibility that resynthesis of the protein could represent a key step also for stable normalization of the renal filter. The recent characterization of the podocin promoter cis- and trans- acting elements and the possibility to characterize low- and high-podocin producer haplotypes offer opportunities to evaluate the capacity for podocin resynthesis in the donor kidney. A review of the literature on posttransplantation recurrence of FSGS in patients originally carrying homozygous and/or heterozygous NPHS2 mutations supports the general idea of a multifactorial origin of the primary disease that can be extended to the pathogenesis of posttransplantation recurrence.