Chronic kidney disease: Biology and Unmet Need

Chronic kidney disease (CKD) is a progressive condition characterized by interconnected pathological processes, including metabolic dysfunction, inflammation, oxidative stress, and renal fibrosis. Growing evidence identifies dysregulated lipid metabolism, particularly intracellular cholesterol accumulation, as a potential contributor to kidney injury. Altered cholesterol homeostasis in glomerular and tubular cells has been linked to cellular stress, inflammation, and renal injury, often alongside broader disturbances in lipid metabolism and mitochondrial function, highlighting cholesterol dysregulation as a promising therapeutic target in CKD.

Current therapies, including RAAS inhibitors, SGLT2 inhibitors, and mineralocorticoid receptor antagonists, have substantially improved kidney protection. Nevertheless, many patients continue to experience progressive loss of renal function. Despite advances in treatments targeting hemodynamic, metabolic, and inflammatory pathways, directly restoring intracellular cholesterol homeostasis remains a relatively unexplored therapeutic approach. Targeting this aspect of renal metabolic dysfunction may therefore provide a complementary strategy to reduce renal injury and potentially slow CKD progression.