Kong Xiangyu, Yuan Hao, Fan Junming, Li Zi, Wu Taixiang, Jiang Lanhui
Department of Epidemiology and Biostatistics, School of Public Health, Chengdu Medical College, Chengdu, China.
Cochrane Database Syst Rev. 2013 Dec 10;2013(12):CD005425. doi: 10.1002/14651858.CD005425.pub2.
Nephrotic syndrome is the collective name given to a group of symptoms that include proteinuria, lipiduria, hypoalbuminaemia, oedema, hypercholesterolaemia, elevated triglycerides, and hyperlipidaemia. Hyperlipidaemia is thought to aggravate glomerulosclerosis (hardening of blood vessels in the kidneys) and enhance progression of glomerular disease. Studies have established that reduction in total cholesterol and low density lipoprotein (LDL) cholesterol is associated with reduction in risk of cardiovascular diseases. In 2011, the European Society of Cardiology and European Atherosclerosis Society guidelines for the management of dyslipidaemia recommended use of statins as first-line agents in the management of nephrotic dyslipidaemia. However, the effectiveness and safety of statins for people with nephrotic syndrome remains uncertain. Furthermore, the efficacy of second-line lipid-lowering drugs, such as ezetimibe and nicotinic acid, has not been proven in patients with nephrotic syndrome who are unable to tolerate statin therapy.
This review aimed to evaluate the benefits and harms of lipid-lowering agents in adults and children with nephrotic syndrome.
We searched the Cochrane Renal Group's Specialised Register (to 18 March 2013) through contact with the Trials Search Co-ordinator using search terms relevant to this review.
All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at participants with nephrotic syndrome that compared any lipid-lowering agent to placebo, no treatment or other lipid-lowering agents, given for not less than four weeks, were included.
Two authors independently assessed study eligibility and risk of bias, and extracted data. Statistical analyses were performed using a random effects model. Dichotomous results were expressed as risk ratios (RR) with 95% confidence intervals (CI). For continuous measures mean difference (MD) was used, or the standardised mean difference (SMD) where different scales had been used.
We included five RCTs enrolling a total of 203 participants. Of these, four studies compared statins with no treatment or placebo, and one compared fibrates with placebo. We found no published studies comparing second-line agents such as ezetimibe, bile acid sequestrants, and nicotinic acid with placebo or no treatment. Our assessment of the risk of bias found that one study was judged overall to be at low risk of bias and the remaining four were judged to be at high risk of bias.Most outcomes were supported by single study data. One study reported significantly increased high density lipoprotein (HDL) cholesterol among participants in the statin arm compared with the no treatment group (MD 5.40 mg/dL, 95% CI 2.31 to 8.49). Another study reported higher serum albumin in the statin group compared to those who received no treatment (MD 0.60 g/dL, 95% CI 0.14 to 1.06). No serious adverse events, such as rhabdomyolysis, were reported, however some minor events occurred. One study reported no significant difference in the number of participants with elevated liver enzymes (RR 3.00, 95% CI 0.13 to 69.52); three studies reported liver enzymes remained within the normal range (no data provided). Four studies reported creatinine phosphokinase (CPK). One study indicated that CPK values fluctuated in both the simvastatin and placebo groups (no data provided); the remaining three studies reported CPK either stayed within the normal range (one study) or there was no significant difference between the lipid lowering agents and placebo.
AUTHORS' CONCLUSIONS: None of the included studies reported patient-centred outcomes including all-cause mortality, cardiovascular mortality, or non-fatal myocardial infarction; only single studies reported cholesterol (HDL, LDL and total cholesterol), triglycerides, serum creatinine, blood urea nitrogen, liver enzymes, and protein (serum, urine). High quality RCTs need to be conducted to assess the safety and efficacy of lipid-lowering drugs for people with nephrotic syndrome.
肾病综合征是一组症状的统称，包括蛋白尿、脂尿、低白蛋白血症、水肿、高胆固醇血症、甘油三酯升高和高脂血症。高脂血症被认为会加重肾小球硬化（肾脏血管硬化）并加速肾小球疾病的进展。研究表明，总胆固醇和低密度脂蛋白（LDL）胆固醇的降低与心血管疾病风险的降低相关。2011年，欧洲心脏病学会和欧洲动脉粥样硬化学会的血脂异常管理指南推荐使用他汀类药物作为治疗肾病性血脂异常的一线药物。然而，他汀类药物对肾病综合征患者的有效性和安全性仍不确定。此外，二线降脂药物，如依泽替米贝和烟酸，在无法耐受他汀类治疗的肾病综合征患者中的疗效尚未得到证实。
本综述旨在评估降脂药物对成人和儿童肾病综合征患者的益处和危害。
我们通过与试验检索协调员联系，使用与本综述相关的检索词，检索了Cochrane肾脏组专业注册库（截至2013年3月18日）。
所有针对肾病综合征患者的随机对照试验（RCT）和半随机对照试验（通过交替、使用交替病历、出生日期或其他可预测方法进行治疗分配的RCT），比较了任何降脂药物与安慰剂、不治疗或其他降脂药物，治疗时间不少于四周，均被纳入。
两位作者独立评估研究的入选资格和偏倚风险，并提取数据。使用随机效应模型进行统计分析。二分结果以风险比（RR）和95%置信区间（CI）表示。对于连续测量，使用平均差（MD），或在使用不同量表时使用标准化平均差（SMD）。
我们纳入了五项RCT，共203名参与者。其中，四项研究比较了他汀类药物与不治疗或安慰剂，一项研究比较了贝特类药物与安慰剂。我们未发现将依泽替米贝、胆汁酸螯合剂和烟酸等二线药物与安慰剂或不治疗进行比较的已发表研究。我们对偏倚风险的评估发现，一项研究总体被判定为低偏倚风险，其余四项被判定为高偏倚风险。大多数结果仅得到单一研究数据的支持。一项研究报告称，与未治疗组相比，他汀类药物组参与者的高密度脂蛋白（HDL）胆固醇显著升高（MD 5.40 mg/dL，95% CI 2.31至8.49）。另一项研究报告称，他汀类药物组的血清白蛋白高于未接受治疗的组（MD 0.60 g/dL，95% CI 0.14至1.06）。未报告严重不良事件，如横纹肌溶解，但发生了一些轻微事件。一项研究报告肝酶升高的参与者数量无显著差异（RR 3.00，95% CI 0.13至69.52）；三项研究报告肝酶保持在正常范围内（未提供数据）。四项研究报告了肌酸磷酸激酶（CPK）。一项研究表明，辛伐他汀组和安慰剂组的CPK值均有波动（未提供数据）；其余三项研究报告CPK要么保持在正常范围内（一项研究），要么降脂药物与安慰剂之间无显著差异。
纳入的研究均未报告以患者为中心的结局，包括全因死亡率、心血管死亡率或非致命性心肌梗死；仅有单一研究报告了胆固醇（HDL、LDL和总胆固醇）、甘油三酯、血清肌酐、血尿素氮、肝酶和蛋白质（血清、尿液）情况。需要开展高质量的RCT来评估降脂药物对肾病综合征患者的安全性和疗效。
