Hodson Elisabeth M, Willis Narelle S, Craig Jonathan C
a) Centre for Kidney Research, The Children's Hospital at Westmead, b) Sydney School of Public Health, The University of Sydney, Locked Bag 4001, Westmead, NSW, Australia, 2145.
Cochrane Database Syst Rev. 2010 Nov 10(11):CD003594. doi: 10.1002/14651858.CD003594.pub4.
The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be treated with immunosuppressive agents including calcineurin inhibitors (cyclosporin or tacrolimus) and with non-immunosuppressive agents such as angiotensin-converting enzyme inhibitors (ACEi). Optimal combinations of these agents with the least toxicity remain to be determined.
To evaluate the benefits and harms of interventions used to treat idiopathic steroid-resistant nephrotic syndrome (SRNS) in children.
Randomised controlled trials (RCTs) were identified from the Cochrane Renal Group's specialised register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles.
RCTs and quasi-RCTs were included if they compared different immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone or other agent given orally or parenterally in children aged three months to 18 years with SRNS.
Two authors independently searched the literature, determined study eligibility, assessed quality and extracted data. For dichotomous outcomes, results were expressed as risk ratios (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model.
Fourteen RCTs (449 children) were included. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission (three studies, 49 children: RR 7.66, 95% CI 1.06 to 55.34). Cyclosporin significantly increased the number with complete or partial remission compared with IV cyclophosphamide (one study, 32 children: RR 3.40, 95% CI 1.12 to 10.28). There was no significant difference in the number who achieved complete remission between oral cyclophosphamide with prednisone versus prednisone alone (two studies, 91 children: RR 1.06, 95% CI 0.61 to 1.87), IV versus oral cyclophosphamide (one study, 11 children: RR 3.13, 95% CI 0.81 to 12.06), IV cyclophosphamide versus oral cyclophosphamide with IV dexamethasone (one study, 49 children: RR 1.13, 95% CI 0.65 to 1.96), tacrolimus versus cyclosporin (one study, 41 children: RR 0.86, 95% CI 0.44 to 1.66) and azathioprine with prednisone versus prednisone alone (one study, 31 children: RR 0.94, 95% CI 0.15 to 5.84). ACEi significantly reduced proteinuria (two studies, 70 children). No studies were identified comparing high dose steroids and cyclosporin with single agents, placebo or no treatment.
AUTHORS' CONCLUSIONS: Further adequately powered, well designed RCTs are needed to confirm the efficacy of cyclosporin and to evaluate other regimens for idiopathic SRNS including high dose steroids with cyclosporin.
大多数首次出现肾病综合征的儿童通过皮质类固醇治疗可实现缓解。治疗无效的儿童可使用免疫抑制剂（包括钙调神经磷酸酶抑制剂（环孢素或他克莫司））和非免疫抑制剂（如血管紧张素转换酶抑制剂（ACEi））进行治疗。这些药物的最佳组合及其最低毒性仍有待确定。
评估用于治疗儿童特发性类固醇抵抗性肾病综合征（SRNS）的干预措施的益处和危害。
从Cochrane肾脏组专业注册库、Cochrane对照试验中心注册库（CENTRAL）、MEDLINE、EMBASE以及文章的参考文献列表中识别随机对照试验（RCT）。
如果RCT和半随机对照试验比较了不同的免疫抑制剂或非免疫抑制剂与安慰剂、泼尼松或其他药物（口服或胃肠外给药）对3个月至18岁患有SRNS的儿童的疗效，则纳入研究。
两位作者独立检索文献、确定研究的合格性、评估质量并提取数据。对于二分法结果，结果以风险比（RR）和95%置信区间（CI）表示。使用随机效应模型汇总数据。
纳入了14项RCT（449名儿童）。与安慰剂或不治疗相比，环孢素显著增加了完全缓解的儿童数量（三项研究，49名儿童：RR 7.66，95%CI 1.06至55.34）。与静脉注射环磷酰胺相比，环孢素显著增加了完全或部分缓解的儿童数量（一项研究，32名儿童：RR 3.40，95%CI 1.12至10.28）。口服环磷酰胺联合泼尼松与单独使用泼尼松相比，完全缓解的儿童数量无显著差异（两项研究，91名儿童：RR 1.06，95%CI 0.61至1.87）；静脉注射与口服环磷酰胺相比（一项研究，11名儿童：RR 3.13，95%CI 0.81至12.06）；静脉注射环磷酰胺与口服环磷酰胺联合静脉注射地塞米松相比（一项研究，49名儿童：RR 1.13，95%CI 0.65至1.96）；他克莫司与环孢素相比（一项研究，41名儿童：RR 0.86，95%CI 0.44至1.66）；硫唑嘌呤联合泼尼松与单独使用泼尼松相比（一项研究，31名儿童：RR 0.94，95%CI 0.15至5.84）。ACEi显著降低蛋白尿（两项研究，70名儿童）。未发现比较高剂量类固醇和环孢素与单一药物、安慰剂或不治疗的研究。
需要进一步进行有足够样本量、设计良好的RCT来确认环孢素的疗效，并评估特发性SRNS的其他治疗方案，包括高剂量类固醇联合环孢素。
