Larkins Nicholas, Kim Siah, Craig Jonathan, Hodson Elisabeth
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Arch Dis Child. 2016 Apr;101(4):404-8. doi: 10.1136/archdischild-2015-308924. Epub 2015 Aug 19.
Nephrotic syndrome is one of the most common paediatric glomerular diseases, with an incidence of around two per 100,000 children per year. Corticosteroids are the mainstay of treatment, with 85%-90% of children going into remission with an 8-week course of treatment. Unfortunately, nephrotic syndrome follows a relapsing and remitting course in the majority, with 90% relapsing at least once. About half will progress to frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Different initial steroid regimens have been evaluated since the first trials in Europe and America in the 1960s. Most trials have been designed to evaluate the optimal duration of the initial therapy, rather than different cumulative doses of corticosteroid, or the management of relapses. Until recently, these data suggested that an initial treatment duration of up to 6 months reduced the number of children developing a relapse, without evidence of increased steroid toxicity. Recently, three large, well-designed randomised control trials were published, which demonstrated no significant reduction in risk of relapse or of developing FRNS by extended treatment compared with 2 or 3 months. While there are few trial data to guide the treatment of individual relapses in steroid-sensitive nephrotic syndrome (SSNS), there is some evidence that a short course of corticosteroid therapy during upper respiratory tract infection may prevent relapse. In patients with FRNS or SDNS who continue to relapse despite low-dose alternate-day steroids a number of non-corticosteroid, steroid-sparing immunosuppressive agents (cyclophosphamide, ciclosporin, tacrolimus, mycophenolate mofetil, levamisole, rituximab) have been shown to reduce the risk of relapse and of FRNS. However, there are limited head-to-head data to inform which agent should be preferred. In this article, we review recent data from randomised trials to update paediatricians on the current evidence supporting interventions in SSNS.
肾病综合征是最常见的儿科肾小球疾病之一，每年每10万名儿童中的发病率约为2例。皮质类固醇是主要的治疗药物，85% - 90%的儿童通过8周疗程的治疗可实现缓解。不幸的是，大多数肾病综合征患儿病情呈复发缓解型，90%的患儿至少复发一次。约一半患儿会进展为频繁复发肾病综合征（FRNS）或激素依赖型肾病综合征（SDNS）。自20世纪60年代欧美首次进行试验以来，不同的初始激素治疗方案已得到评估。大多数试验旨在评估初始治疗的最佳时长，而非皮质类固醇的不同累积剂量或复发的管理。直到最近，这些数据表明初始治疗时长长达6个月可减少复发患儿数量，且无激素毒性增加的证据。最近，三项大型、设计良好的随机对照试验发表，结果显示与2或3个月的治疗相比，延长治疗并未显著降低复发风险或发展为FRNS的风险。虽然几乎没有试验数据可指导激素敏感型肾病综合征（SSNS）个体复发的治疗，但有证据表明上呼吸道感染期间短期使用皮质类固醇治疗可能预防复发。对于尽管使用低剂量隔日激素仍持续复发的FRNS或SDNS患者，一些非皮质类固醇、激素节省型免疫抑制剂（环磷酰胺、环孢素、他克莫司、霉酚酸酯、左旋咪唑、利妥昔单抗）已被证明可降低复发风险和FRNS的发生风险。然而，可供参考哪种药物更优的直接对比数据有限。在本文中，我们回顾了随机试验的最新数据，以便向儿科医生更新支持SSNS干预措施的当前证据。
