Néphrologie Pédiatrique et centre de référence MARHEA, Hôpital Necker-Enfants Malades, APHP, Université Paris Descartes, Paris, France.
Am J Kidney Dis. 2010 May;55(5):923-7. doi: 10.1053/j.ajkd.2009.12.026. Epub 2010 Mar 3.
We report 3 children with atypical hemolytic uremic syndrome associated with anti-complement factor H (CFH) autoantibodies who presented with sustained remission with low antibody titers and normal kidney function after plasma exchanges (PEs) and cyclophosphamide pulses. The 3 children initially presented with acute vomiting, fatigue, gross hematuria, hypertension, hemolytic anemia, thrombocytopenia, nephrotic syndrome, and acute kidney injury. C3 levels were normal in patients 1 and 3 and low in patient 2 (0.376 mg/mL [0.376 g/L]). CFH antibody titers were increased (15,000 to > 32,000 arbitrary units [AU]). Patient 1, an 11-year-old boy, was treated with 12 PEs, leading to a decrease in CFH antibody titer (to 800 AU). A first relapse 1 month later was treated with 6 PEs and 4 rituximab infusions. A second relapse 3 months later required 5 PEs, and the patient received oral steroids (0.5 mg/d/kg body weight) and 5 cyclophosphamide pulses (1 g/1.73 m(2)), leading to sustained remission with normal kidney function (estimated glomerular filtration rate [eGFR], 120 mL/min/1.73 m(2) [2.0 mL/s/1.73 m(2)]) and a stable decrease in CFH antibody titer (to 2,000 AU) 3 years later. Patient 2, a 5-year-old boy, required dialysis therapy for 2 weeks. He received 3 plasma infusions without remission. Six PEs associated with 2 cyclophosphamide pulses (0.5 g/1.73 m(2)) and steroids (1 mg/d/kg body weight) led to rapid remission, with eGFR of 107 mL/min/1.73 m(2) [1.78 mL/s/1.73 m(2)] and a prolonged decrease in CFH antibody titer after 15 months (1,300 AU). Patient 3, a 16-month-old boy, was treated with oral steroids (1 mg/d/kg body weight), 2 PEs, and 2 cyclophosphamide pulses (0.5 g/1.73 m(2)), resulting in a stable decrease in CFH antibody titer to 276 AU. Kidney function quickly normalized (eGFR, 110 mL/min/1.73 m(2) [1.83 mL/s/1.73 m(2)]) and has remained normal after 14 months. All 3 patients show a homozygous deletion mutation of the CFHR1 and CFHR3 genes. Cyclophosphamide pulses with PE may lead to a prolonged decrease in CFH antibody titers and a favorable outcome of atypical hemolytic uremic syndrome and kidney function.
我们报告了 3 例与抗补体因子 H (CFH) 自身抗体相关的非典型溶血性尿毒症综合征患儿，他们在接受血浆置换 (PE) 和环磷酰胺脉冲治疗后，抗体滴度较低且肾功能正常，病情持续缓解。这 3 名患儿最初表现为急性呕吐、疲劳、肉眼血尿、高血压、溶血性贫血、血小板减少、肾病综合征和急性肾损伤。患者 1 和 3 的 C3 水平正常，患者 2 的 C3 水平较低 (0.376 mg/mL [0.376 g/L])。CFH 抗体滴度升高 (15,000 至 >32,000 个任意单位 [AU])。患者 1 是一名 11 岁男孩，接受了 12 次 PE，导致 CFH 抗体滴度下降 (至 800 AU)。1 个月后首次复发，接受了 6 次 PE 和 4 次利妥昔单抗输注。3 个月后第二次复发，需要 5 次 PE，患者接受了口服类固醇 (0.5 mg/d/kg 体重) 和 5 次环磷酰胺脉冲治疗 (1 g/1.73 m(2))，此后肾功能正常 (估算肾小球滤过率 [eGFR]，120 mL/min/1.73 m(2) [2.0 mL/s/1.73 m(2)])，CFH 抗体滴度稳定下降 (至 2,000 AU)，3 年后仍持续缓解。患者 2 是一名 5 岁男孩，需要透析治疗 2 周。他接受了 3 次血浆输注，但未缓解。6 次 PE 联合 2 次环磷酰胺脉冲 (0.5 g/1.73 m(2)) 和类固醇 (1 mg/d/kg 体重) 迅速缓解，15 个月后 eGFR 为 107 mL/min/1.73 m(2) [1.78 mL/s/1.73 m(2)]，CFH 抗体滴度持续下降 (至 1,300 AU)。患者 3 是一名 16 个月大的男孩，接受了口服类固醇 (1 mg/d/kg 体重)、2 次 PE 和 2 次环磷酰胺脉冲治疗 (0.5 g/1.73 m(2))，此后 CFH 抗体滴度稳定下降至 276 AU。肾功能迅速恢复正常 (eGFR，110 mL/min/1.73 m(2) [1.83 mL/s/1.73 m(2)])，14 个月后仍保持正常。所有 3 例患者均存在 CFHR1 和 CFHR3 基因的纯合缺失突变。PE 联合环磷酰胺脉冲可能导致 CFH 抗体滴度持续下降，并改善非典型溶血性尿毒症综合征和肾功能。
