BACKGROUND Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening microangiopathy, frequently causing kidney failure. Inhibition of the terminal complement complex with eculizumab is the only licensed treatment but mostly requires long-term administration and risks severe side effects. The underlying genetic cause of aHUS is thought to influence the severity of initial and recurring episodes, with milder courses in patients with mutations in membrane cofactor protein (MCP). METHODS Twenty pediatric cases of aHUS due to isolated heterozygous MCP mutations were reported from 12 German pediatric nephrology centers to describe initial presentation, timing of relapses, treatment, and kidney outcome. RESULTS The median age of onset was 4.6 years, with a female to male ratio of 1:3. Without eculizumab maintenance therapy, 50% (9/18) of the patients experienced a first relapse after a median period of 3.8 years. Kaplan-Meier analysis showed a relapse-free survival of 93% at 1 year. Four patients received eculizumab long-term treatment, while 3 patients received short courses. We could not show a benefit from complement blockade therapy on long term kidney function, independent of short-term or long-term treatment. To prevent 1 relapse with eculizumab, the theoretical number-needed-to-treat (NNT) was 15 for the first year and 3 for the first 5 years after initial presentation. CONCLUSION Our study shows that heterozygous MCP mutations cause aHUS with a risk of first relapse of about 10% per year, resulting in large NNTs for prevention of relapses with eculizumab. More studies are needed to define an optimal treatment schedule for patients with MCP mutations to minimize the risks of the disease and treatment.

中文翻译：

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由于 MCP 突变而长期治疗 aHUS 的不同方法：多中心分析。

背景非典型溶血性尿毒症综合征 (aHUS) 是一种罕见的、危及生命的微血管病，经常导致肾功能衰竭。用依库珠单抗抑制终末补体复合物是唯一获得许可的治疗方法，但大多需要长期给药并有严重副作用的风险。aHUS 的潜在遗传原因被认为会影响初始和复发发作的严重程度，膜辅因子蛋白 (MCP) 突变患者的病程较轻。方法 12 个德国儿科肾脏病中心报告了 20 例由孤立的杂合 MCP 突变引起的 aHUS 儿科病例，以描述最初的表现、复发的时间、治疗和肾脏结果。结果 中位发病年龄为 4.6 岁，男女之比为 1:3。如果没有依库珠单抗维持治疗，50% (9/18) 的患者在中位时间为 3.8 年后首次复发。Kaplan-Meier 分析显示 1 年无复发生存率为 93%。4 名患者接受依库珠单抗长期治疗，3 名患者接受短期治疗。我们无法证明补体阻断疗法对长期肾功能的益处，与短期或长期治疗无关。为防止依库珠单抗 1 次复发，理论需要治疗数 (NNT) 在第一年为 15 次，在初次就诊后的前 5 年为 3 次。结论 我们的研究表明，杂合的 MCP 突变导致 aHUS，每年首次复发的风险约为 10%，导致使用依库珠单抗预防复发的大量 NNT。