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Endothelin and Tubulointerstitial Renal Disease

  • 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 shownAll 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. (C) 2015 Elsevier Inc. All rights reserved.show moreshow less

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Metadaten
Author:Albert C. M. Ong, Karoline von Websky, Berthold HocherGND
DOI:https://doi.org/10.1016/j.semnephrol.2015.03.004
ISSN:0270-9295 (print)
ISSN:1558-4488 (online)
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25966351
Parent Title (English):Seminars in nephrology
Publisher:Elsevier
Place of publication:Philadelphia
Document Type:Review
Language:English
Year of first Publication:2015
Year of Completion:2015
Release Date:2017/03/27
Tag:ADPKD; ET-1; ETA; ETB; Endothelin; acute kidney injury; polycystic kidney disease
Volume:35
Issue:2
Pagenumber:11
First Page:197
Last Page:207
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
Peer Review:Referiert