Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Centre, Homburg/Saar, Germany.
Nephrol Dial Transplant. 2019 Aug 1;34(8):1266-1271. doi: 10.1093/ndt/gfz122.
Chronic kidney disease (CKD) is associated with a substantially increased risk for the development of atherosclerotic cardiovascular (CV) disease. Accordingly, CV mortality is increased even in the earliest stages of CKD. In the general population and in CKD patients, high plasma levels of low-density lipoprotein cholesterol (LDL-C) are crucially involved in the initiation and progression of atherosclerotic vascular lesions. Lowering LDL-C by use of statins and/or ezetimibe represents the gold standard of lipid-lowering therapy, with a great body of evidence from several large clinical trials. Statin therapy reduces CV events in patients with normal and impaired kidney function alike, while the evidence for patients on maintenance haemodialysis is weaker. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease represents a novel lipid-lowering tool. Currently the monoclonal antibodies evolocumab and alirocumab are the approved PCSK9 inhibitors. Despite maximum-tolerated statin therapy, they efficiently further reduce LDL-C plasma levels without any major adverse effects. Moreover, in large clinical outcome trials, both antibodies have been proven to lower CV events. Notably, the LDL-lowering capacity was independent of baseline kidney function and also efficient in patients with moderate CKD. However, patients with severely impaired kidney function, that is, the population at the highest CV risk, have been excluded from those trials. The relevance of the LDL-independent effects of PCSK9 inhibitors, such as lowering lipoprotein(a) or ameliorating dyslipidaemia in patients with nephrotic syndrome, has to be determined. Therefore further specific studies assessing the effects and outcomes of PCSK9-inhibiting treatment in CKD patients are warranted.
慢性肾脏病（CKD）与动脉粥样硬化性心血管（CV）疾病的发生风险显著增加有关。因此，即使在 CKD 的早期阶段，CV 死亡率也会增加。在普通人群和 CKD 患者中，血浆中低密度脂蛋白胆固醇（LDL-C）水平升高与动脉粥样硬化血管病变的发生和进展密切相关。使用他汀类药物和/或依折麦布降低 LDL-C 是降脂治疗的金标准，多项大型临床试验提供了大量证据。他汀类药物治疗可降低肾功能正常和受损患者的 CV 事件发生率，而维持性血液透析患者的证据较弱。脯氨酰肽链内切酶枯草溶菌素/克那霉 9（PCSK9）丝氨酸蛋白酶抑制剂代表了一种新型的降脂工具。目前，单克隆抗体依洛尤单抗和阿利西尤单抗是已批准的 PCSK9 抑制剂。尽管进行了最大耐受剂量的他汀类药物治疗，但它们能有效进一步降低 LDL-C 血浆水平，且无任何重大不良反应。此外，在大型临床结局试验中，这两种抗体都已被证明能降低 CV 事件。值得注意的是，LDL 降低能力与基线肾功能无关，在中度 CKD 患者中也有效。然而，那些肾功能严重受损的患者（即 CV 风险最高的人群）被排除在这些试验之外。PCSK9 抑制剂的 LDL 非依赖性作用的相关性，如降低脂蛋白（a）或改善肾病综合征患者的血脂异常，仍有待确定。因此，需要进一步开展特定的研究，评估 CKD 患者中 PCSK9 抑制治疗的效果和结局。
