PCSK9: Its Role in Lipid Metabolism and as a Novel Target for the Treatment of Metabolic Kidney Disease
Year: 2025
Type: article
Abstract: INTRODUCTION: The interplay between lipid metabolism and renal injury in the context of metabolic kidney diseases has garnered growing scientific interest. Nevertheless, the majority of existing studies have primarily concentrated on the modulation of individual lipid parameters, with relatively limited emphasis on the potential role of PCSK9 as a crucial mediator linking lipid metabolism disturbances to kidney damage. METHODS: A comprehensive literature search was performed across databases such as PubMed and Web of Science, covering the period from 2003 to 2025. Search terms included "PCSK9," "metabolic kidney disease," and "chronic kidney disease", which were used to identify relevant Randomized Controlled Trials (RCTs), systematic reviews, and mechanistic studies. In addition, proteomics data were obtained from the iProX database and integrated into the analysis. RESULTS: PCSK9 exacerbates lipid metabolism dysregulation through LDLR degradation. Its inhibitors improve lipid metabolism and reduce proteinuria, thereby exerting renoprotective effects via downregulation of lipid-related proteins (e.g., Angptl3) and inhibition of TGF-β signaling components. DISCUSSION: PCSK9 as a therapeutic target, extending prior research by demonstrating dual lipidrenal protective effects. However, evidence for rare metabolic kidney diseases and long-term safety data is lacking. CONCLUSION: PCSK9 inhibitors show promise in metabolic kidney diseases, but large-scale trials are needed to clarify their long-term efficacy and optimal application scope.
Source: Current Vascular Pharmacology
Authors: Hongqian Li, Ling Qi, Dongmei Zhang, Santao OU, Weihua Wu
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4414529320