Injectable Lipid-Lowering Therapies in Advanced Chronic Kidney Disease: Efficacy, Safety and the Dialysis Paradox.

Abstract

Cardiovascular (CV) disease represents the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), particularly in those with advanced stages and dialysis dependence. Dyslipidemia is highly prevalent in this population and displays distinct features, substantially affected by multiple factors such inflammation and dialysis modality. Although statins remain the cornerstone of lipid-lowering therapy in earlier CKD stages, their benefit becomes less certain in advanced disease and predominantly end-stage kidney disease. This phenomenon, termed the dialysis paradox, is further confounded by reverse epidemiology, wherein lower cholesterol paradoxically associates with worse outcomes due to malnutrition and inflammation. Injectable lipid-lowering therapies, including proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (evolocumab, alirocumab), small interfering RNA (inclisiran), and emerging agents targeting ANGPTL3, apolipoprotein C-III, and lipoprotein(a), offer novel mechanisms of action with pharmacokinetic profiles largely preserved across CKD stages. Available evidence demonstrates substantial low-density lipoprotein (LDL) reduction without renal toxicity, though patients with advanced CKD and dialysis dependence remain critically underrepresented in clinical trials. Current guidelines diverge significantly for dialysis populations, reflecting this persistent evidence gap. This review synthesizes the biological rationale, pharmacologic properties, and available clinical evidence for injectable lipid-lowering therapies in advanced CKD. Moreover, it highlights why their integration into the care of this high-risk population merits serious consideration - not only for their potent and durable lipid-lowering effects, but also for their ability to target other paths that contribute to the excess CV risk not captured by LDL alone. However, key unresolved questions require dedicated investigation.