Lipids and PCSK9 inhibition in chronic kidney disease

The prevalence of chronic kidney diseases (CKD) is steadily increasing worldwide. Patients with CKD show a massively increased cardiovascular mortality. Lipoproteins, among other things play an important role in the development of CKD-associated atherosclerotic cardiovascular diseases. Lipoproteins in uremic patients show alterations of the molecular structure, which result in significant changes of the biological function. This is the case for low-density lipoproteins (LDL) as well as high-density lipoproteins (HDL), the vasoprotective properties of which are lost and they are transformed into lipoproteins that have negative vascular effects. Moreover, triglyceride-rich lipoproteins induce a sterile inflammation reaction potentially leading to vascular and organ damage. In 2019, novel guidelines for the treatment of dyslipidemia with new LDL-cholesterol (LDL-C) targets were published by the European Society of Cardiology (ECS) and the European Atherosclerosis Society (EAS). In summary, more stringent lowering of LDL-C is recommended. Besides lifestyle modifications and treatment with statins/ezetimibe, proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors provide a promising additional treatment option. In patients with mild to moderate limitations of kidney function, PCSK9 inhibition is safe and similarly effective as treatment in the general population. Currently, specific studies in patients with more advanced CKD are lacking. Overall, lowering of LDL-C plays an important role in primary and secondary prevention of cardiovascular diseases in patients with CKD.