Lipid-Lowering Therapies in Patients with Chronic Kidney Disease: A Perspective on High-Density Lipoprotein Cholesterol

Chronic kidney disease (CKD) increases the risk of cardiovascular disease (CVD), with dyslipidemia being a contributing risk factor. In patients with CKD, diminished antioxidant, anti-inflammatory, and cholesterol transport capacities of high-density lipoprotein cholesterol (HDL-C) may contribute to atherosclerosis and poor CVD outcomes. Different lipid-lowering therapies (LLTs) have demonstrated efficacy in correcting dyslipidemia in patients without kidney disease, including substantial elevations in HDL-C levels with triglyceride-lowering therapies, such as fibrates and niacin, as well as novel HDL-targeted therapies, including cholesterol-ester transfer protein inhibitors. However, the effects of HDL-elevating therapies in populations without kidney disease may not readily be extrapolated to patients with CKD, given the distinct dyslipidemia patterns and the lack of high-quality clinical trials in this population. Despite plausible mechanisms of HDL-elevation to improve clinical outcomes, current clinical guidelines only recommend statin use for the treatment of hyperlipidemia in patients with non–dialysis-dependent CKD. In this narrative review, we discuss how HDL-C functionality is affected in patients with CKD and explore evidence investigating different LLTs for HDL elevation and improved clinical outcomes in this population. In patients with CKD, we recommend further investigation of HDL-targeted therapies, comparative effectiveness evaluation of HDL-elevating LLTs versus statins across various clinical endpoints, and whether HDL-C elevation mediates these outcomes.