Endothelial Dysfunction and Therapeutic Advances in Chronic Kidney Disease

ABSTRACT Chronic kidney disease (CKD) substantially increases cardiovascular risk, with endothelial dysfunction as its central pathological mechanism. This review summarises the molecular regulatory mechanisms underlying endothelial dysfunction in CKD and highlights recent advances in treatment strategies. The pathophysiology of endothelial injuries involves a complex network of multiple factors and mechanisms, including oxidative stress, inflammation, glycocalyx damage, ischaemia, hypoxia, cellular senescence and endothelial‐mesenchymal transition (EndMT). Recent advances have yielded several promising CKD treatment strategies, including dual endothelin‐angiotensin receptor antagonists (DEARA), dipeptidyl peptidase‐4 inhibitors (DPP‐4i), glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), renin‐angiotensin‐aldosterone system inhibitors (RAASi), sodium‐glucose cotransporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRA), which have demonstrated favourable protective effects on endothelial cells. Moreover, emerging anti‐ageing therapies are novel therapeutic directions for research related to endothelial protection. In future studies, the synergistic effects of nonpharmacological interventions (such as lifestyle modifications and nutritional support) and pharmacological therapies will be a new direction, providing ideas for improving endothelial dysfunction, decelerating the progression of CKD, reducing the risk of cardiovascular events, and ultimately improving patient outcomes.