Determinants of circulating PCSK9 levels and the efficacy of PCSK9 inhibitor therapies in chronic kidney disease: a systematic review

PURPOSE OF REVIEW: Chronic kidney disease (CKD) significantly increases the risk of atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia-particularly elevated low-density lipoprotein cholesterol (LDL-C)-being a shared risk factor. While statin-based therapies are effective in early-stage CKD, their benefits in dialysis and kidney transplant patients remain inconclusive. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of lipid metabolism. This review aims to summarize the factors influencing PCSK9 levels in CKD patients and evaluate the safety and efficacy of PCSK9 inhibitors across different stages of CKD. RECENT FINDINGS: Multiple factors have been associated with variations in plasma PCSK9 concentrations in CKD, including glycemic status, proteinuria, renal function, dialysis modality, lipid-lowering therapy, and circadian rhythms. PCSK9 inhibitors, such as alirocumab, evolocumab, and inclisiran, effectively reduce LDL-C and ASCVD risk in patients with mild-to-moderate CKD. However, evidence is limited in patients with advanced CKD (stages 4-5, end stage renal disease (ERSD)), particularly those undergoing dialysis. Elevated PCSK9 levels may not independently predict ASCVD risk in CKD populations. Nonetheless, PCSK9 inhibitors provide a well-tolerated and effective lipid-lowering option in early CKD. Large-scale prospective studies are warranted to clarify their role in patients with ESRD.