Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors
Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors
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DOI：
10.1016/j.kint.2019.01.023
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发表时间：
2019-06-01
影响因子：
19.6
通讯作者：
Fakhouri, Fadi
中科院分区：
文献类型：
--
作者：
Le Clech, Alice;Simon-Tillaux, Noemie;Fakhouri, Fadi
继发性溶血性尿毒症综合征(HUS)是一组与各种潜在疾病相关的血栓性微血管病变。它是否属于补体介导的HUS仍存在争议。我们分析了110例继发性HUS患者的补体基因罕见变异的表现、结局和频率，这些患者可归因于药物(29%)、自身免疫性疾病(24%)、感染(17%)、恶性肿瘤(10%)、肾小球疾病(9%)、肾外器官移植(8%)和胰腺炎(3%)。补体基因罕见变异的频率在继发性HUS患者(5%)和健康人(法国和欧洲对照组分别为6%和8%)中相似。确诊时，40%的患者需要透析，18%的患者有神经症状。50%的患者接受了血浆治疗，35%的患者接受了eculizumab治疗。血液学和肾脏完全缓解率分别为80%和24%。39%的患者进展为慢性肾脏疾病(3-4期)，另外37%的患者发展为终末期肾脏疾病。11%的患者死亡，最常见的是HUS潜在原因的并发症。只有一名患者经历了HUS复发。与未接受eculizumab治疗的患者相比，接受eculizumab治疗的患者出现了更严重的HUS，并且在诊断时更有可能需要透析。两组的血液学缓解率、慢性肾脏病(3-4期)和终末期肾病的发生率相似。继发性HUS是一种急性非复发性HUS，与补体调节失调无关。在这种情况下，eculizumab的疗效尚未确定。
Secondary hemolytic uremic syndrome (HUS) is a heterogeneous group of thrombotic microangiopathies associated with various underlying conditions. Whether it belongs to the spectrum of complement-mediated HUS remains controversial. We analysed the presentation, outcome, and frequency of complement gene rare variants in a cohort of 110 patients with secondary HUS attributed to drugs (29%), autoimmune diseases (24%), infections (17%), malignancies (10%), glomerulopathies (9%), extra-renal organ transplantation (8%), and pancreatitis (3%). The frequency of complement gene rare variants was similar in patients with secondary HUS (5%) and in healthy individuals (6% and 8% in French and European controls, respectively). At diagnosis, 40% of patients required dialysis and 18% had neurological manifestations. Fifty percent of patients received plasmatherapy and 35% were treated with eculizumab. Haematological and complete renal remission was achieved in 80% and 24% of patients, respectively. Thirty-nine percent of patients progressed to chronic kidney disease (stages 3-4) and an additional 37% reached end-stage renal disease. Eleven percent of patients died, most often from complications of the underlying cause of HUS. Only one patient experienced an HUS relapse. Patients treated with eculizumab presented with more severe HUS and were more likely to require dialysis at the time of diagnosis as compared to patients not treated with eculizumab. Rates of hematological remission, chronic kidney disease (stages 3-4), and end-stage renal disease were similar in the two groups. Secondary HUS is an acute nonrelapsing form of HUS, not related to complement dysregulation. The efficacy of eculizumab in this setting is not yet established.