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Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children
发布于：2013年10月14日 文字：【大】【中】【小】
Kidney Int. 2013 Oct 2. doi: 10.1038/ki.2013.373. [Epub ahead of print]
Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children.
Sinha A, Gulati A, Saini S, Blanc C, Gupta A, Gurjar BS, Saini H, Kotresh ST, Ali U, Bhatia D, Ohri A, Kumar M, Agarwal I, Gulati S, Anand K, Vijayakumar M, Sinha R, Sethi S, Salmona M, George A, Bal V, Singh G, Dinda AK, Hari P, Rath S, Dragon-Durey MA, Bagga A.
Source
Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Abstract
Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000?AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS.
H因子抗体的产生是导致HUS发生的一种不常见的原因。儿童患者的临床特征及预后的资料有限。我们进行了一个多中心的研究，纳入了138例H因子抗体相关的印度HUS患儿，共占总体HUS患者的56%。患儿血浆H因子抗体的滴度较高(均值为 7054 AU/ml)，并与C3水平呈负相关，但与H因子水平无相关性。在68例患儿中，发生CFHR1纯合缺失的患者有60例。治疗方案包括透析(119例)、血浆置换(105例)以及静脉注射免疫球蛋白(26例)。87例患儿接受免疫抑制治疗，采用口服强的松疗法，其中一些患儿还同时采用了静注环磷酰胺或者利妥昔单抗治疗。随着血浆置换治疗的进行，抗体滴度可迅速降低。疾病复发时，抗体滴度升高。随访3个月时，36例患儿发生了主要终点事件(CKD4-5或者死亡)。最后一次随访时，有41例患儿发生了主要终点事件，112例可追踪到的患儿中，有14例出现了疾病的复发。主要终点事件发生的独立危险因素为抗体滴度高于8000?AU/ml、低C3水平及血浆置换治疗延迟。血浆置换治疗联合免疫抑制治疗可提高肾脏生存率：平均2.6个患儿中可减少一个主要终点事件的发生。强的松加霉酚酸酯或者硫唑嘌呤的维持性免疫抑制治疗可显著降低疾病的复发。因此，免疫抑制治疗及血浆置换治疗的正确使用对于改善抗H因子抗体阳性的HUS患儿的预后是有益的。