Endothelin and tubulointerstitial renal disease

• Published in: Seminars in nephrology Vol. 35; no. 2; p. 197
• Main Authors: Ong, Albert C M, von Websky, Karoline, Hocher, Berthold
• Format: Journal Article
• Language: English
• Published: United States 01.03.2015
• Subjects: Animals; Disease Progression; Endothelins - metabolism; Glomerular Filtration Rate - physiology; Humans; Kidney Tubules - metabolism; Kidney Tubules - pathology; Nephritis, Interstitial - metabolism; Nephritis, Interstitial - pathology; Nephritis, Interstitial - physiopathology; ADPKD; ET(A); ET(B); ET-1; Endothelin; polycystic kidney disease; acute kidney injury
• ISSN: 1558-4488
• DOI: 10.1016/j.semnephrol.2015.03.004

All components of the endothelin (ET) system are present in renal tubular cells. In this review, we summarize current knowledge about ET and the most common tubular diseases: acute kidney injury (AKI) and polycystic kidney disease. AKI originally was called acute tubular necrosis, pointing to the most prominent morphologic findings. Similarly, cysts in polycystic kidney disease, and especially in autosomal-dominant polycystic kidney disease, are of tubular origin. Preclinical studies have indicated that the ET system and particularly ETA receptors are involved in the pathogenesis of ischemia-reperfusion injury, although these findings have not been translated to clinical studies. The ET system also has been implicated in radiocontrast-dye-induced AKI, however, ET-receptor blockade in a large human study was not successful. The ET system is activated in sepsis models of AKI; the effectiveness of ET blocking agents in preclinical studies is variable depending on the model and the ET-receptor antagonist used. Numerous studies have shown that the ET system plays an important role in the complex pathophysiology associated with cyst formation and disease progression in polycystic kidney disease. However, results from selective targeting of ET-receptor subtypes in animal models of polycystic kidney disease have proved disappointing and do not support clinical trials. These studies have shown that a critical balance between ETA and ETB receptor action is necessary to maintain structure and function in the cystic kidney. In summary, ETs have been implicated in the pathogenesis of several renal tubulointerstitial diseases, however, experimental animal findings have not yet led to use of ET blockers in human beings.