An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document
An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document
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DOI：
10.1016/j.nefro.2015.07.005
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发表时间：
2015-01-01
期刊：
影响因子：
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通讯作者：
Rodríguez de Córdoba, Santiago
中科院分区：
文献类型：
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作者：
Campistol, Josep M.;Arias, Manuel;Rodríguez de Córdoba, Santiago
溶血性尿毒综合征（HUS）是一种由非免疫性溶血性贫血、血小板减少和急性肾功能衰竭三联征组成的临床实体，其基础病变由系统性血栓性微血管病（TMA）介导。不同的原因可以诱发以HUS为特征的TMA过程。在本文中，我们认为非典型HUS（阿胡斯）是HUS的一种亚型，其中TMA现象是由于补体系统的活性失调而导致的肾脏和其他器官的微血管系统中的内膜损伤的结果。近年来，在补体系统基因中发现了多种与aHUS相关的突变，这些突变可以解释约60%的阿胡斯病例，并且许多突变和多态性已被功能性表征。这些发现已经确定阿胡斯是细胞表面上补体的活化调节不足的结果，导致C5和补体末端途径介导的内膜损伤。依库珠单抗是一种单克隆抗体，可抑制C5的活化并阻断促炎分子C5 a的产生和细胞膜攻击复合物的形成。在阿胡斯患者的前瞻性研究中，使用依库珠单抗显示出快速和持续中断TMA过程，并且与肾功能的显著长期改善、血浆治疗的中断和透析需求的重要减少相关。根据现有文献和积累的临床经验，西班牙阿胡斯小组发表了一份共识文件，其中包括对阿胡斯治疗的建议（Nefrologia 2013;33[1]：27-45）。在本文件的当前在线版本中，我们更新了TMA的病因分类、阿胡斯的病理生理学、鉴别诊断和治疗管理。(C)2015年，西班牙语协会Nefrologia。出版社：Elsevier Espana，S.L.U.
Haemolytic uraemic syndrome (HUS) is a clinical entity defined as the triad of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). Different causes can induce the TMA process that characterizes HUS. In this document we consider atypical HUS (aHUS) a sub-type of HUS in which the TMA phenomena are the consequence of the endotelial damage in the microvasculature of the kidneys and other organs due to a disregulation of the activity of the complement system. In recent years, a variety of aHUs-related mutations have been identified in genes of the the complement system, which can explain approximately 60% of the aHUS cases, and a number of mutations and polymorphisms have been functionally characterized. These findings have stablished that aHUS is a consequence of the insufficient regulation of the activiation of the complement on cell surfaces, leading to endotelial damage mediated by C5 and the complement terminal pathway. Eculizumab is a monoclonal antibody that inhibits the activation of C5 and blocks the generation of the pro-inflammatory molecule C5a and the formation of the cell membrane attack complex. In prospective studies in patients with aHUS, the use of Eculizumab has shown a fast and sustained interruption of the TMA process and it has been associated with significative long-term improvements in renal function, the interruption of plasma therapy and important reductions in the need of dialysis. According to the existing literature and the accumulated clinical experience, the Spanish aHUS Group published a consensus document with recommendations for the treatment of aHUs (Nefrologia 2013;33[1]:27-45). In the current online version of this document, we update the aetiological classification of TMAs, the pathophysiology of aHUS, its differential diagnosis and its therapeutic management. (C) 2015 Sociedad Espanola de Nefrologia. Published by Elsevier Espana, S.L.U.