PDF(Pubmed)
Abstract：
IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis. It is a heterogeneous disease with different presentations and high morbidity. Thirty per cent of adults and 20% of children (followed into adulthood) will have a 50% decline in kidney function or develop kidney failure after 10 years.
To determine the benefits and harms of immunosuppressive therapy for the treatment of IgAN in children.
We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 03 October 2023 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) investigating the treatment of IgAN in children with immunosuppressive therapies compared to placebo, no treatment, supportive care, standard therapy (Japanese protocol), other immunosuppressive therapies or non-immunosuppressive therapies.
Two authors independently extracted data and assessed the risk of bias. Random effects meta-analyses were used to summarise estimates of treatment effects. Treatment effects were expressed as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and the mean difference (MD) and 95% CI for continuous outcomes. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs and the ROBIN-I tool for NRSIs. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).
This review included 13 studies with 686 participants. Ten RCTs included 334 children and 191 adults, and three NRSIs included 151 participants, all children. Most participants had mild kidney disease. The risk of bias was unclear for most of the domains relating to allocation concealment, blinding of participants, personnel, and outcome assessment. In children with IgAN, it is uncertain if corticosteroid (steroid) therapy, compared to placebo reduces proteinuria (1 study, 64 children and young adults: RR 0.47, 95% CI 0.13 to 1.72; low certainty evidence) or the decline in estimated glomerular filtration rate (eGFR) (1 study, 64 children and young adults: RR 0.47, 95% CI 0.09 to 2.39; low certainty evidence). It is uncertain if steroids reduce proteinuria compared to supportive care (2 studies, 61 children: RR 0.04, 95% CI -0.83 to 0.72; low certainty evidence). Adverse events associated with steroid therapy were not assessed due to heterogeneity in steroid protocols, including dose and duration, and lack of systematic assessment for adverse events in the included studies. Azathioprine, mycophenolate mofetil, mizoribine, or cyclophosphamide alone or in combination with steroid therapy had uncertain effects on improving proteinuria or preventing eGFR decline in children with IgAN. Fish oil, vitamin E and tonsillectomy had uncertain effects on improving proteinuria or preventing eGFR decline. Effects of other immunosuppressive therapies, secondary outcomes and adverse events were not assessed due to insufficient data.
There is a lack of high-quality evidence to guide the management of IgAN in children. There is no evidence to indicate that steroids, other immunosuppressive therapies, or tonsillectomy, when added to optimal supportive care, prevent a decline in eGFR or proteinuria in children with IgAN. Available studies were few, with small numbers, low-quality evidence, high or uncertain risk of bias, did not systematically assess harms associated with treatment, or report net benefits or harms. Severe cases and atypical presentations of IgAN were not included in the reviewed studies, and our findings cannot be generalised to these situations.
To determine the benefits and harms of immunosuppressive therapy for the treatment of IgAN in children.
We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 03 October 2023 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) investigating the treatment of IgAN in children with immunosuppressive therapies compared to placebo, no treatment, supportive care, standard therapy (Japanese protocol), other immunosuppressive therapies or non-immunosuppressive therapies.
Two authors independently extracted data and assessed the risk of bias. Random effects meta-analyses were used to summarise estimates of treatment effects. Treatment effects were expressed as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and the mean difference (MD) and 95% CI for continuous outcomes. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs and the ROBIN-I tool for NRSIs. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).
This review included 13 studies with 686 participants. Ten RCTs included 334 children and 191 adults, and three NRSIs included 151 participants, all children. Most participants had mild kidney disease. The risk of bias was unclear for most of the domains relating to allocation concealment, blinding of participants, personnel, and outcome assessment. In children with IgAN, it is uncertain if corticosteroid (steroid) therapy, compared to placebo reduces proteinuria (1 study, 64 children and young adults: RR 0.47, 95% CI 0.13 to 1.72; low certainty evidence) or the decline in estimated glomerular filtration rate (eGFR) (1 study, 64 children and young adults: RR 0.47, 95% CI 0.09 to 2.39; low certainty evidence). It is uncertain if steroids reduce proteinuria compared to supportive care (2 studies, 61 children: RR 0.04, 95% CI -0.83 to 0.72; low certainty evidence). Adverse events associated with steroid therapy were not assessed due to heterogeneity in steroid protocols, including dose and duration, and lack of systematic assessment for adverse events in the included studies. Azathioprine, mycophenolate mofetil, mizoribine, or cyclophosphamide alone or in combination with steroid therapy had uncertain effects on improving proteinuria or preventing eGFR decline in children with IgAN. Fish oil, vitamin E and tonsillectomy had uncertain effects on improving proteinuria or preventing eGFR decline. Effects of other immunosuppressive therapies, secondary outcomes and adverse events were not assessed due to insufficient data.
There is a lack of high-quality evidence to guide the management of IgAN in children. There is no evidence to indicate that steroids, other immunosuppressive therapies, or tonsillectomy, when added to optimal supportive care, prevent a decline in eGFR or proteinuria in children with IgAN. Available studies were few, with small numbers, low-quality evidence, high or uncertain risk of bias, did not systematically assess harms associated with treatment, or report net benefits or harms. Severe cases and atypical presentations of IgAN were not included in the reviewed studies, and our findings cannot be generalised to these situations.
摘要：
背景：IgA肾病（IgAN）是原发性肾小球肾炎的最常见原因。它是一种异质性疾病，具有不同的表现和高发病率。30％的成年人和20％的儿童（随后进入成年期）将在10年后肾功能下降50％或发展为肾衰竭。
目的：探讨免疫抑制治疗儿童IgAN的利弊。
方法：我们联系了信息专家，并使用与本评论相关的搜索词搜索了截至2023年10月3日的Cochrane肾脏和移植研究注册。登记册中的研究是通过对CENTRAL的搜索确定的，MEDLINE,和EMBASE,会议记录,国际临床试验注册平台(ICTRP)搜索门户，和ClinicalTrials.gov.
方法：我们纳入了随机对照试验（RCT）和非随机干预研究（NRSIs），研究了与安慰剂相比，免疫抑制治疗儿童IgAN的治疗。没有治疗,支持性护理,标准疗法（日本方案），其他免疫抑制疗法或非免疫抑制疗法。
方法：两位作者独立提取数据并评估偏倚风险。随机效应荟萃分析用于总结治疗效果的估计。治疗效果以风险比（RR）和95%置信区间（CI）表示，以及连续结局的平均差(MD)和95%CI。使用Cochrane偏倚风险工具评估RCT偏倚风险，使用ROBIN-I工具评估NRSIs偏倚风险。使用建议分级评估证据的确定性，评估,发展,和评价（等级）。
结果：本综述包括13项研究，有686名参与者。十个RCT包括334名儿童和191名成人，三名NRSIs包括151名参与者，所有的孩子。大多数参与者患有轻度肾脏疾病。与分配隐藏有关的大多数领域的偏见风险尚不清楚，致盲参与者，人员,和结果评估。在有IgAN的孩子中，尚不确定皮质类固醇（类固醇）治疗，与安慰剂相比，蛋白尿减少(1项研究，64名儿童和年轻人：RR0.47，95％CI0.13至1.72；低确定性证据）或估计肾小球滤过率（eGFR）的下降（1项研究，64名儿童和年轻人：RR0.47，95%CI0.09至2.39；低确定性证据）。与支持治疗相比，类固醇是否能减少蛋白尿还不确定(2项研究，61名儿童：RR0.04，95%CI-0.83至0.72；低确定性证据）。由于类固醇方案的异质性，未评估与类固醇治疗相关的不良事件。包括剂量和持续时间，纳入研究缺乏对不良事件的系统评估。硫唑嘌呤,霉酚酸酯，mizoribine,或环磷酰胺单独或联合类固醇治疗对改善IgAN患儿的蛋白尿或预防eGFR下降的效果不确定.鱼油,维生素E和扁桃体切除术对改善蛋白尿或预防eGFR下降的效果不确定.其他免疫抑制疗法的效果，由于数据不足,次要结局和不良事件未进行评估.
结论：缺乏指导儿童IgAN治疗的高质量证据。没有证据表明类固醇,其他免疫抑制疗法，或者扁桃体切除术,当添加到最佳支持性护理中时，预防IgAN患儿eGFR下降或蛋白尿。现有的研究很少，数字很小，低质量的证据,高或不确定的偏见风险，没有系统地评估与治疗相关的危害，或报告净收益或危害。IgAN的严重病例和非典型表现未包括在审查的研究中。我们的发现不能推广到这些情况。
目的：探讨免疫抑制治疗儿童IgAN的利弊。
方法：我们联系了信息专家，并使用与本评论相关的搜索词搜索了截至2023年10月3日的Cochrane肾脏和移植研究注册。登记册中的研究是通过对CENTRAL的搜索确定的，MEDLINE,和EMBASE,会议记录,国际临床试验注册平台(ICTRP)搜索门户，和ClinicalTrials.gov.
方法：我们纳入了随机对照试验（RCT）和非随机干预研究（NRSIs），研究了与安慰剂相比，免疫抑制治疗儿童IgAN的治疗。没有治疗,支持性护理,标准疗法（日本方案），其他免疫抑制疗法或非免疫抑制疗法。
方法：两位作者独立提取数据并评估偏倚风险。随机效应荟萃分析用于总结治疗效果的估计。治疗效果以风险比（RR）和95%置信区间（CI）表示，以及连续结局的平均差(MD)和95%CI。使用Cochrane偏倚风险工具评估RCT偏倚风险，使用ROBIN-I工具评估NRSIs偏倚风险。使用建议分级评估证据的确定性，评估,发展,和评价（等级）。
结果：本综述包括13项研究，有686名参与者。十个RCT包括334名儿童和191名成人，三名NRSIs包括151名参与者，所有的孩子。大多数参与者患有轻度肾脏疾病。与分配隐藏有关的大多数领域的偏见风险尚不清楚，致盲参与者，人员,和结果评估。在有IgAN的孩子中，尚不确定皮质类固醇（类固醇）治疗，与安慰剂相比，蛋白尿减少(1项研究，64名儿童和年轻人：RR0.47，95％CI0.13至1.72；低确定性证据）或估计肾小球滤过率（eGFR）的下降（1项研究，64名儿童和年轻人：RR0.47，95%CI0.09至2.39；低确定性证据）。与支持治疗相比，类固醇是否能减少蛋白尿还不确定(2项研究，61名儿童：RR0.04，95%CI-0.83至0.72；低确定性证据）。由于类固醇方案的异质性，未评估与类固醇治疗相关的不良事件。包括剂量和持续时间，纳入研究缺乏对不良事件的系统评估。硫唑嘌呤,霉酚酸酯，mizoribine,或环磷酰胺单独或联合类固醇治疗对改善IgAN患儿的蛋白尿或预防eGFR下降的效果不确定.鱼油,维生素E和扁桃体切除术对改善蛋白尿或预防eGFR下降的效果不确定.其他免疫抑制疗法的效果，由于数据不足,次要结局和不良事件未进行评估.
结论：缺乏指导儿童IgAN治疗的高质量证据。没有证据表明类固醇,其他免疫抑制疗法，或者扁桃体切除术,当添加到最佳支持性护理中时，预防IgAN患儿eGFR下降或蛋白尿。现有的研究很少，数字很小，低质量的证据,高或不确定的偏见风险，没有系统地评估与治疗相关的危害，或报告净收益或危害。IgAN的严重病例和非典型表现未包括在审查的研究中。我们的发现不能推广到这些情况。
