The vicious circle of chronic kidney disease and hypertriglyceridemia: What is first, the hen or the egg?

• Published in: Atherosclerosis Vol. 403; p. 119146
• Main Authors: Tramontano, Daniele, D'Erasmo, Laura, Larouche, Miriam, Brisson, Diane, Lauzière, Alex, Di Costanzo, Alessia, Bini, Simone, Minicocci, Ilenia, Covino, Stella, Baratta, Francesco, Pasquali, Marzia, Cerbelli, Bruna, Gaudet, Daniel, Arca, Marcello
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.04.2025
• Subjects: Animals; Chronic kidney disease (CKD); Chylomicrons (CM); Humans; Hypertriglyceridemia (HTG); Hypertriglyceridemia - blood; Hypertriglyceridemia - complications; Hypertriglyceridemia - epidemiology; Hypertriglyceridemia - metabolism; Kidney - metabolism; Kidney - pathology; Kidney - physiopathology; Lipid Metabolism; Lipotoxicity; Oxidative Stress; Podocytes; Proteinuria; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - epidemiology; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - physiopathology; Risk Factors; Triglycerides - blood; Triglycerides - metabolism; Hypertriglyceridemia (HTG); Podocytes; Chylomicrons (CM); Lipotoxicity; Chronic kidney disease (CKD); Proteinuria
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2025.119146

Chronic kidney disease (CKD) is documented to cause alterations in lipid metabolism, and this was considered a potent driver of increased cardiovascular risk. Among the diverse alteration of lipid traits in CKD, research endeavours have predominantly concentrated on low-density lipoproteins (LDL) in view of the potent pro-atherogenic role of these lipoprotein particles and the demonstration of protective cardiovascular effect of reducing LDL. However, few studies have focused on the metabolism of triglyceride-rich lipoproteins and even fewer on their role in causing kidney damage. Therefore, the comprehensive description of the impact of hypertriglyceridemia (HTG) in CKD pathophysiology remains largely undetermined. This reflects the difficulty of disentangling the independent role of triglycerides (TG) in the complex, bidirectional relationship between TG and kidney disease. Abnormal neutral lipid accumulation in the intrarenal vasculature and renal cells eventually due to HTG may also promote glomerular injury, throughout mechanisms including oxidative stress, mitochondrial dysfunction and proinflammatory responses. While epidemiological and experimental evidence suggests a potential role of TG in kidney damage, the causal mechanisms and their clinical relevance remain unclear, representing a significant area for future investigation. This review aims to highlight the intricate interplay between TG metabolism and kidney disease, shedding light on the mechanisms through which HTG may influence kidney functionality. [Display omitted] •CKD contributes to HTG through lipolytic enzyme deficiencies, impairing lipid clearance and raising kidney damage risk.•Epidemiological, experimental and genetic studies support the role of HTG in favoring renal damage and CKD progression.•Inherited lipid disorders like LPG, LCAT deficiency worsen renal health.•Kidney lipotoxicity triggers inflammation and cell dysfunction, thus promoting and/or aggravating renal damage.