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The contribution of vascular endothelium to the progression of chronic kidney disease

Michael S Goligorsky

Although historically endothelial contribution to chronic kidney disease (CKD) had been neglected, recent investigations provide conclusive evidence of its role in maintaining tissue homeostasis, supporting tissue regeneration and, when dysfunctional, instigating development and progression of tissue fibrosis. These findings are of critical importance for the development of nephrosclerosis and progression of CKD. Three endothelial pathways involved in the progression of CKD include stress-induced premature senescence of endothelial cells, endothelial-mesenchymal transition, and the loss of the endothelial surface layer. These abnormalities orchestrate the development of proteinuria, pro-inflammatory microenvironment, microvascular rarefaction, pro-fibrotic state, and regenerative failure. Therapeutic strategies to overcome endothelial cell dysfunction and its renal consequences will be discussed.