Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, is effective and safe in the treatment of hyperlipidemia in chronic kidney disease stage 3 – 4

AIMS: To evaluate the efficacy and safety of evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in chronic kidney disease (CKD). BACKGROUND: Dyslipidemia is common in patients with CKD and contributes to their elevated cardiovascular risk. However, evidence regarding the lipid-lowering efficacy and renal safety of PCSK9 inhibitors in CKD stages 3 - 4 is limited. MATERIALS AND METHODS: A cohort of 200 patients with stage 3 - 4 CKD and hyperlipidemia were administered evolocumab in a single-center retrospective study. Lipid parameters including low-density lipoprotein cholesterol (LDL-C), renal function (estimated glomerular filtration rate, serum creatinine, blood urea nitrogen), and liver enzymes were assessed at baseline and at 3, 6, and 12 months follow-up. Subgroup and multivariate analyses were performed to determine factors associated with LDL-C reduction. Publicly available transcriptomic resources were consulted to provide biological parameters regarding tissue-specific PCSK9 expression. RESULTS: After 12 months, LDL-C was significantly decreased (-56.3 ± 10.5%) compared to baseline where the reduction in stages 3 and stage 4 CKD were similar. Non-high-density lipoprotein (HDL-C) and total cholesterol also declined significantly, but here were no significant changes in HDL-C and triglycerides. Renal function showed no significant deterioration, and no hepatotoxicity or clinically significant adverse events occurred. Baseline LDL-C and age were independent predictors of LDL-C reduction. Public transcriptomic data indicated that PCSK9 expression is predominantly enriched in liver tissue but remains minimal in renal tissues and across major renal cell types, providing biological evidence to explain the preserved renal function observed in this cohort. CONCLUSION: Evolocumab is an effective agent for lowering LDL-C levels and has a satisfactory short-term renal and hepatic safety in this cohort with similar effects across CKD subgroups. The low renal expression of PCSK9 may partly explain its renal safety. These results support the use of evolocumab as a practical and well-tolerated lipid-lowering option for CKD patients who need intensive LDL-C control.