Hypertriglyceridemia in chronic kidney disease: pathophysiological mechanisms, cardiovascular risk, and emerging therapeutics

Hypertriglyceridemia (HTG) is highly prevalent among patients with chronic kidney disease (CKD) and plays a critical role in both the progression of nephropathy and the increased risk of cardiovascular events. The underlying pathophysiology involves metabolic disturbances of triglyceride (TG)-rich lipoproteins, leading to lipid accumulation within renal cells. This accumulation triggers lipotoxicity, oxidative stress, and inflammatory cascades that ultimately contribute to renal fibrosis. In advanced stages of CKD, statins demonstrate limited efficacy, whereas emerging therapeutic agents show promising potential. RNA-based gene therapies targeting apolipoprotein C-III and angiopoietin-like protein 3 effectively reduce TG levels while maintaining a favorable renal safety profile. Additionally, agents such as pemafibrate, PCSK9 inhibitors, sodium–glucose cotransporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists not only lower lipid levels but also confer significant cardiorenal protective effects. Consequently, the management of HTG in CKD should transition from a singular lipid-lowering focus to a comprehensive, stratified approach that targets the interconnected pathways of lipotoxicity, inflammation, and fibrosis, with the ultimate goal of improving cardiorenal outcomes.