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Review
. 2024 Oct 11;13(20):6056.
doi: 10.3390/jcm13206056.

Endothelin Inhibitors in Chronic Kidney Disease: New Treatment Prospects

Agata Rakotoarison  1 , Marta Kepinska  2 , Andrzej Konieczny  1 , Karolina Władyczak  3 , Dariusz Janczak  4 , Agnieszka Hałoń  3 , Piotr Donizy  3 , Mirosław Banasik  1
Affiliations
Review

Endothelin Inhibitors in Chronic Kidney Disease: New Treatment Prospects

Agata Rakotoarison et al. J Clin Med. .

Abstract

The endothelin system is reported to play a significant role in glomerular and tubulointerstitial kidney disease. In the kidney, endothelins are produced in mesangial cells and the glomerular basement membrane by the endothelium and podocytes. The endothelin system regulates glomerular function by inducing proliferation, increasing permeability and in effect proteinuria, and stimulating inflammation, tubular fibrosis, and glomerular scarring. Endothelin A receptor antagonists have been proven to delay the progression of chronic kidney disease and play a protective role in immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and diabetic nephropathy. There are several ongoing research studies with ETAR antagonists in nondiabetic nephropathy, Alport disease, vasculitis and scleroderma nephropathy, which results are promising. Some reports suggest that the endothelin system might contribute to ischemia-reperfusion injury, acute graft rejection and deterioration of graft function. Endothelin inhibition in renal transplantation and its influence on graft survival is the future direction needing further research. The most frequent side effects associated with ETAR antagonists is fluid retention. Additionally, it should be considered if selective ETAR antagonists therapy needs to be co-administered with sodium-glucose co-transporter 2 inhibitors, renin-angiotensin-aldosterone inhibitors or diuretics and which patients should be recruited to such treatment to minimize the risk of adverse outcomes.

Keywords: ETAR; ETBR; FSGS; Nephropathy IgA; chronic kidney disease; diabetic nephropathy; endothelins; proteinuria.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The scheme presents vascular endothelin pathway. MLCK—myosin light-chain kinase, CaM—calmodulin, PIP2—phosphatidylinositol 4,5-bisphosphate, IP3—inositol trisphosphate, DAG—diacylglycerol, SR—sarcoplasmatic reticulum, ECE—endothelin converting enzyme, PLC—phospholipase C, PGI2—prostaglandin I2. The illustration was made in Adobe Illustrator Program.
Figure 2
Figure 2
The scheme presents the endothelin system pathway in glomeruli. MCP1—monocyte chemoattractant protein-1. The illustration was made in Adobe Illustrator Program.
Figure 3
Figure 3
The scheme presents the endothelin system pathway in renal medullary. The illustration was made in Adobe Illustrator Program. The arrows with “×” means blockade of water and sodium reabsorption.
See this image and copyright information in PMC

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