Renoprotective effects of ETA receptor antagonists therapy in experimental non-diabetic chronic kidney disease: Is there still hope for the future?

Title:

Renoprotective effects of ETA receptor antagonists therapy in experimental non-diabetic chronic kidney disease: Is there still hope for the future?

Creator:

Ivana Vaněčková, Silvie Hojná, Josef Zicha, Luděk Červenka, Libor Kopkan, Vernerová, Z., and Michaela Kadlecová

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:a77d83e5-b076-434e-8a9a-53f064f90cd6
uuid:a77d83e5-b076-434e-8a9a-53f064f90cd6
issn:0862-8408

Subject:

fyziologie člověka, human physiology, Endothelin A receptor blockade, End-organ damage, Chronic kidney disease, Proteinuria, Diuretics, RAS blockade, 14, and 612

Type:

model:article and TEXT

Format:

print, bez média, and svazek

Description:

Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ETA) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ETA receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD. Unfortunately, fluid retention encountered in large clinical trials in diabetic CKD led to the termination of these studies. Therefore, several advances, including the synthesis of new antagonists with enhanced pharmacological activity, the use of lower doses of ET antagonists, the addition of diuretics, plus simply searching for distinct pathological states to be treated, are promising targets for future experimental studies. In support of these approaches, our group demonstrated in adult subtotally nephrectomized Ren-2 transgenic rats that the addition of a diuretic on top of renin-angiotensin and ETA blockade led to a further decrease of proteinuria. This effect was independent of blood pressure which was normalized in all treated groups. Recent data in non-diabetic CKD, therefore, indicate a new potential for ETA antagonists, at least under certain pathological conditions., I. Vaněčková, S. Hojná, M. Kadlecová, Z. Vernerová, L. Kopkan, L. Červenka, J. Zicha., and Seznam literatury

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2018 Volume:67 | Number:Suppl 1

Harvested from:

CDK

Metadata only:

false