Dyslipidaemia in nephrotic syndrome: mechanisms and treatment.
Dyslipidaemia in nephrotic syndrome: mechanisms and treatment.
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DOI：
10.1038/nrneph.2017.155
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Smoyer WE
中科院分区：
文献类型：
--
作者：
Agrawal S;Zaritsky JJ;Fornoni A;Smoyer WE
肾病综合征是一种高度流行的疾病，尽管其治疗取得了显著进展，但其发病率仍很高。肾病综合征的许多并发症，包括动脉粥样硬化和血栓栓塞风险增加，可能与脂质代谢失调和血脂异常有关。这些异常包括胆固醇、甘油三酯和含载脂蛋白B的脂蛋白VLDL和IDL的血浆水平升高;内皮、肌肉和脂肪组织中脂蛋白脂肪酶活性降低;肝脂肪酶活性降低;以及酶PCSK 9水平升高。此外，未成熟HDL颗粒的血浆水平增加，胆固醇流出减少。过去几年的研究显著提高了我们对肾病综合征相关血脂异常的分子发病机制的认识，也提高了我们对心血管并发症、进行性肾脏疾病和血栓栓塞相关加重风险的认识。尽管缺乏明确的治疗指南，但越来越多地使用各种策略，包括他汀类药物、胆汁酸螯合剂、贝特类药物、烟酸和依折麦布以及脂质单采术，这些策略似乎也在相当大比例的患者中诱导肾病综合征的部分或完全临床缓解。未来潜在的治疗可能还包括使用最近开发的抗PCSK 9单克隆抗体和小抑制RNA抑制PCSK 9，以及靶向新发现的肾病综合征中失调的脂质代谢分子调节剂。
Nephrotic syndrome is a highly prevalent disease that is associated with high morbidity despite notable advances in its treatment. Many of the complications of nephrotic syndrome, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol, triglycerides and the apolipoprotein B containing lipoproteins VLDL and IDL; decreased lipoprotein lipase activity in the endothelium, muscle and adipose tissues; decreased hepatic lipase activity; and increased levels of the enzyme PCSK9. In addition, there is an increase in the plasma levels of immature HDL particles and reduced cholesterol efflux. Studies from the past few years have markedly improved our understanding of the molecular pathogenesis of nephrotic syndrome associated dyslipidaemia, and also heightened our awareness of the associated exacerbated risks of cardiovascular complications, progressive kidney disease and thromboembolism. Despite the absence of clear guidelines regarding treatment, various strategies are being increasingly utilized, including statins, bile acid sequestrants, fibrates, nicotinic acid and ezetimibe, as well as lipid apheresis, which seem to also induce partial or complete clinical remission of nephrotic syndrome in a substantial percentage of patients. Future potential treatments will likely also include inhibition of PCSK9 using recently developed anti PCSK9 monoclonal antibodies and small inhibitory RNAs, as well as targeting newly identified molecular regulators of lipid metabolism that are dysregulated in nephrotic syndrome.
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发表时间：
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