Atypical hemolytic uremic syndrome.
Atypical hemolytic uremic syndrome.
复制标题
DOI：
10.1186/1750-1172-6-60
复制
发表时间：
2011-09-08
影响因子：
3.7
通讯作者：
Frémeaux-Bacchi V
中科院分区：
文献类型：
--
作者：
Loirat C;Frémeaux-Bacchi V
溶血性尿毒综合征（HUS）是由机械性溶血性贫血、血小板减少和肾损害三联征定义的。非典型HUS（阿胡斯）定义为非志贺毒素HUS，即使一些作者包括由于肺炎链球菌或其他原因引起的继发性阿胡斯，阿胡斯也表示由于补体旁路途径调节障碍引起的原发性疾病。非典型溶血尿毒综合征占儿童溶血尿毒综合征的5 - 10%，但占成人溶血尿毒综合征的大多数。补体-aHUS的发病率尚不确切。然而，已经报告了超过1000例针对补体异常进行调查的阿胡斯患者。发病时间为新生儿期至成年期。大多数患者表现为溶血性贫血、血小板减少和肾衰竭，20%的患者有肾外表现。2 - 10%的患者在第一次发病时死亡，三分之一的患者在第一次发病时进展为终末期肾衰竭。一半的病人会复发。编码补体调节蛋白因子H、膜辅因子蛋白（MCP）、因子I或血栓调节蛋白的基因突变已分别在20- 30%、5- 15%、4-10%和3-5%的患者中证实，C3转化酶蛋白、C3和因子B的基因突变分别在2-10%和1- 4%的患者中证实。此外，6-10%的患者有抗H因子抗体。阿胡斯的诊断依赖于1）无相关疾病2）无志贺毒素-HUS的标准（粪便培养和志贺毒素的PCR;抗脂多糖抗体的血清学）3）无血栓性血小板减少性紫癜的标准（血清ADAMTS 13活性> 10%）。需要对补体系统进行研究（C3、C4、H因子和I因子血浆浓度、白细胞上MCP表达和抗H因子抗体;遗传筛查以确定风险因素）。该疾病在大约20%的家系中是家族性的，具有常染色体隐性或显性传播模式。由于该病的发病率为50%，遗传咨询很困难。血浆疗法一直是一线治疗，直到目前，没有毫无疑问的效率证明。移植后复发的风险很高，但MCP-HUS除外。病例报告和两项II期试验显示，补体C5阻断剂依库珠单抗的疗效令人印象深刻，这表明它将成为下一个标准治疗。除了接受强化血浆疗法或依库珠单抗治疗的患者外，预后最差的是因子H-HUS，因为死亡率可达20%，50%的幸存者没有恢复肾功能。半数I-HUS因子进展为终末期肾衰竭。相反，大多数MCP-HUS患者的肾功能得以保留。抗H因子抗体-HUS如果早期治疗有良好的结果。
Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently, without unquestionable demonstration of efficiency. There is a high risk of post-transplant recurrence, except in MCP-HUS. Case reports and two phase II trials show an impressive efficacy of the complement C5 blocker eculizumab, suggesting it will be the next standard of care. Except for patients treated by intensive plasmatherapy or eculizumab, the worst prognosis is in factor H-HUS, as mortality can reach 20% and 50% of survivors do not recover renal function. Half of factor I-HUS progress to end-stage renal failure. Conversely, most patients with MCP-HUS have preserved renal function. Anti-factor H antibodies-HUS has favourable outcome if treated early.