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Review
. 2015 May 25;4(6):1171-92.
doi: 10.3390/jcm4061171.

Endothelin Blockade in Diabetic Kidney Disease

Lidia Anguiano  1 , Marta Riera  2   3 , Julio Pascual  4   5 , María José Soler  6   7
Affiliations
Review

Endothelin Blockade in Diabetic Kidney Disease

Lidia Anguiano et al. J Clin Med. .

Abstract

Diabetic kidney disease (DKD) remains the most common cause of chronic kidney disease and multiple therapeutic agents, primarily targeted at the renin-angiotensin system, have been assessed. Their only partial effectiveness in slowing down progression to end-stage renal disease, points out an evident need for additional effective therapies. In the context of diabetes, endothelin-1 (ET-1) has been implicated in vasoconstriction, renal injury, mesangial proliferation, glomerulosclerosis, fibrosis and inflammation, largely through activation of its endothelin A (ETA) receptor. Therefore, endothelin receptor antagonists have been proposed as potential drug targets. In experimental models of DKD, endothelin receptor antagonists have been described to improve renal injury and fibrosis, whereas clinical trials in DKD patients have shown an antiproteinuric effect. Currently, its renoprotective effect in a long-time clinical trial is being tested. This review focuses on the localization of endothelin receptors (ETA and ETB) within the kidney, as well as the ET-1 functions through them. In addition, we summarize the therapeutic benefit of endothelin receptor antagonists in experimental and human studies and the adverse effects that have been described.

Keywords: diabetic kidney disease (DKD); endothelin A receptor (ETA receptor); endothelin B receptor (ETB receptor); endothelin receptor antagonists; endothelin-1 (ET-1).

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Figures

Figure 1
Figure 1
Schematic representation of functional ET-1 receptors in the kidney. Glomerulus (podocytes and mesangial cells) express primarily ETA receptors. In renal microcirculation both ETA and ETB receptors are expressed. Renal tubules contain mainly ETB receptors, with more expression in the thick ascending limb and the collecting duct.
Figure 2
Figure 2
Effects of ET-1 on the kidney. ET-1 through ETA receptors has vasoconstrictor, pro-inflammatory and podocyte-injury related effects. ET-1 activation through ETB receptors leads to vasodilation and activation of NO pathway.
See this image and copyright information in PMC

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