PCSK9 Inhibitors: A Potential Priority Choice for Lipid Management in Patients with Diabetic Kidney Disease.

Abstract

Diabetic kidney disease (DKD), a severe microvascular complication of diabetes mellitus (DM), is the predominant cause of end-stage renal disease. Patients with DM frequently experience dyslipidemia, which can exacerbate DKD progression. Consequently, initiating aggressive lipid-lowering therapy in the early stages of DKD is as important as controlling blood glucose and reducing urinary protein. Statins have been the cornerstone of lipid management, but their use is often limited by adverse effects and potential risks of accelerating DKD progression with prolonged administration. As such, identifying optimal lipid management agents for patients with DKD remains an urgent clinical priority. As a pivotal enzyme in lipid metabolism, proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in lipid regulation and is intricately linked to various biological processes, including inflammation, programmed cell death (apoptosis, autophagy, pyroptosis, and ferroptosis), and tumor immunity. Emerging evidence suggests that PCSK9 is involved in the occurrence and development of DKD. This article reviews the possible pathways through which PCSK9 is involved in DKD from the aspects of inflammation, oxidative stress, and programmed cell death and how PCSK9 inhibitors may have the potential to improve DKD while reducing cholesterol levels. Therefore, we propose that PCSK9 inhibitors can be a potential priority choice for lipid-lowering in patients with DKD.