Gilbert Rodney D, Al-Dakkak Imad, Boothe Clare, Cobb Timothy E, Gale Daniel P, Griffin Sian, Marks Stephen D, Scully Marie, Shenoy Mohan, Waters Aoife, Sheerin Neil S
Southampton Children's Hospital, Southampton, UK.
Alexion AstraZeneca Rare Disease, Boston, USA.
BMC Nephrol. 2025 Aug 5;26(1):434. doi: 10.1186/s12882-025-04321-x.
Atypical haemolytic uraemic syndrome (aHUS) is a rare kidney disease characterized by thrombotic microangiopathy. This study presents the first analysis of UK patients enrolled in the Global aHUS Registry, focusing on patient characteristics and disease natural history prior to treatment initiation (n = 172; 74 paediatric, 98 adult). Mean age at first aHUS manifestation was 23.6 years overall (4.9 years for paediatric patients, 37.8 years for adults). Additional thrombotic microangiopathy events occurred in 57.0% of patients between initial clinical suspicion and registry enrolment. Potential precipitating factors were recorded in 14.0% of patients. Of 115 patients at active sites, 90.4% had genetic data recorded, with 73.8% undergoing "complete" genetic testing (results entered for C3, CD46, CFH, CFB and CFI, as a minimum). Of those with genetic data available, 52.9% had an identified pathogenic variant. Gastrointestinal involvement was the most common extra-renal manifestation, presenting in 22.2% of patients. End-stage kidney disease (ESKD) was present in 8.7% at baseline. ESKD-free survival probability at five years was 0.80 for paediatric patients and 0.57 for adults. ESKD-free survival was negatively influenced by CFH, C3, or CFI variants. This study highlights the historically poor prognosis for untreated patients with aHUS. The UK population of the Global aHUS Registry represents a valuable research cohort with comprehensive demographic data and high genetic characterization. These findings underscore the importance of early aHUS identification and intervention to prevent ESKD and improve patient outcomes.
非典型溶血尿毒综合征（aHUS）是一种以血栓性微血管病为特征的罕见肾脏疾病。本研究首次对纳入全球aHUS注册登记的英国患者进行了分析，重点关注治疗开始前的患者特征和疾病自然史（n = 172；74例儿科患者，98例成人）。首次出现aHUS的总体平均年龄为23.6岁（儿科患者为4.9岁，成人患者为37.8岁）。在初始临床怀疑至登记入组期间，57.0%的患者发生了额外的血栓性微血管病事件。14.0%的患者记录到了潜在的诱发因素。在115个活跃位点的患者中，90.4%有基因数据记录，其中73.8%进行了“完整”的基因检测（至少录入了C3、CD46、CFH、CFB和CFI的结果）。在有可用基因数据的患者中，52.9%有已确定的致病变异。胃肠道受累是最常见的肾外表现，22.2%的患者出现该症状。基线时8.7%的患者存在终末期肾病（ESKD）。儿科患者五年无ESKD生存概率为0.80，成人为0.57。CFH、C3或CFI变异对无ESKD生存有负面影响。本研究强调了未经治疗的aHUS患者既往预后较差。全球aHUS注册登记中的英国人群是一个具有全面人口统计学数据和高基因特征的宝贵研究队列。这些发现强调了早期识别和干预aHUS以预防ESKD并改善患者预后的重要性。
