Chronic kidney disease (CKD) is a global health problem with a profound impact on quality of life. Cardiovascular disease is established as a major cause of morbidity and mortality in patients with CKD. Dyslipidemia is frequently observed in CKD patients, suggesting a causal relation between dyslipidemia and cardiovascular disease in CKD patients. Currently, lipid-lowering drugs such as statins, are the primary choice for lipid lowering therapy in high-risk populations. Despite many studies showing CVD risk reduction with statins, CVD still remains the leading cause of the death in CKD. This underscores the need for new therapeutic approaches to reduce cardiovascular risk in CKD patients. Reduced lipoprotein lipase activity, increased very low-density lipoprotein production, increased proprotein convertase subtilisin kexin type 9 (PCSK9) expression and loss of hepatic heparan sulfate proteoglycans (HSPG) syndecan-1 have been associated with CKD-related dyslipidemia. Low-density lipoprotein receptor (LDLR), low-density lipoprotein receptor-related protein 1 (LRP-1) and syndecan-1, are the most important hepatic receptors for lipoprotein clearance. However, their contributions to the pathogenesis of dyslipidemia and cardiovascular disease in CKD remain unclear. Interestingly, in CKD, increased plasma lipid levels are associated with elevated levels of PCSK9. This promotes the proteolysis of LDLR, suggesting a role for PCSK9 in CKD-associated dyslipidemia. Fully humanized monoclonal antibodies targeting PCSK9 have been approved by the US Food and Drug Administration and the European Medicines Agency as lipid lowering treatment for patients with hypercholesterolemia. In CKD sub-group analysis, ODYSSEY COMBO I and ODYSSEY COMBO II studies demonstrated strong reduction in LDL-C by alirocumab compared to placebo and ezetimibe and when added to statins. However, their efficacy in reducing plasma TG is controversial. Therefore, further research work is need for a detailed analysis on efficacy and safety of PCSK9 antibodies in CKD groups. Interestingly, novel findings on PCSK9 interaction with HSPG might shed new insight on altered lipid metabolism in CKD. In this review, we discuss various aspects of lipoprotein metabolism and hepatic lipoprotein receptor signaling pathways along with the concept of renal disease-related dyslipidemia. Furthermore, this review highlights the drawbacks of current lipid-lowering therapies and proposes novel approaches for lipid management in CKD.

慢性肾脏病（CKD）是一个全球性健康问题，对生活质量产生深远影响。心血管疾病被确定为CKD患者发病和死亡的主要原因。在CKD患者中经常观察到血脂异常，这表明CKD患者的血脂异常与心血管疾病之间存在因果关系。目前，降脂药物如他汀类药物是高危人群降脂治疗的主要选择。尽管许多研究表明他汀类药物可降低CVD的风险，但CVD仍然仍然是CKD死亡的主要原因。这强调了需要新的治疗方法来降低CKD患者的心血管风险。脂蛋白脂肪酶活性降低，极低密度脂蛋白产生增加，CKD相关血脂异常与增加的9型前蛋白转化酶枯草杆菌蛋白酶kexin（PCSK9）表达和肝硫酸硫酸乙酰肝素蛋白聚糖（HSPG）syndecan-1的丢失有关。低密度脂蛋白受体（LDLR），低密度脂蛋白受体相关蛋白1（LRP-1）和syndecan-1是清除脂蛋白最重要的肝受体。然而，它们在CKD中血脂异常和心血管疾病的发病机理中的作用仍不清楚。有趣的是，在CKD中，血浆脂质水平升高与PCSK9水平升高有关。这促进了LDLR的蛋白水解，提示PCSK9在CKD相关血脂异常中的作用。靶向PCSK9的完全人源化单克隆抗体已获得美国食品药品监督管理局和欧洲药品管理局的批准，可作为高胆固醇血症患者的降脂治疗。在CKD子组分析中，ODYSSEY COMBO I和ODYSSEY COMBO II研究表明，与安慰剂和依折麦布相比，当与他汀类药物合用时，alirocumab可显着降低LDL-C。然而，它们在降低血浆TG方面的功效是有争议的。因此，需要进一步的研究工作来详细分析CKD组中PCSK9抗体的功效和安全性。有趣的是，有关PCSK9与HSPG相互作用的新发现可能为CKD脂质代谢改变提供了新的见解。在这篇评论中，我们讨论了脂蛋白代谢和肝脂蛋白受体信号传导途径的各个方面，以及与肾脏疾病相关的血脂异常的概念。此外，本综述突出了当前降脂疗法的弊端，并提出了CKD中脂质治疗的新方法。