Key result
Endothelin receptor antagonists have shown utility in reducing blood pressure, proteinuria, and arterial stiffness in chronic kidney disease, though their clinical use is limited by fluid retention.
Why the study?
Endothelin-1 is hypothesized to influence the progression of chronic kidney disease, prompting this review of its pathophysiology and the role of endothelin receptor antagonists.
Do endothelin receptor antagonists improve outcomes in patients with chronic kidney disease?
Do endothelin receptor antagonists improve outcomes in patients with chronic kidney disease?
Endothelin receptor antagonists show promise in reducing proteinuria and slowing tissue damage in various forms of chronic kidney disease, though fluid retention remains a significant safety concern.
Fluid retention precludes routine use in CKD; leaves open targeted trials addressing safety.
BACKGROUND: Endothelins (ET) are a family of peptides that act as potent vasoconstrictors and pro-fibrotic growth factors. ET-1 is integral to renal and cardiovascular pathophysiology and exerts effects via autocrine, paracrine and endocrine signaling pathways tied to regulation of aldosterone, catecholamines, and angiotensin. In the kidney, ET-1 is critical to maintaining renal perfusion and controls glomerular arteriole tone and hemodynamics. It is hypothesized that ET-1 influences the progression of chronic kidney disease (CKD), and the objective of this review is to discuss the pathophysiology, and role of ET and endothelin receptor antagonists (ERAs) in CKD. SUMMARY: The use of ERAs in hypertensive nephropathy has the potential to decrease proteinuria, and in diabetic nephropathy has the potential to restore glycocalyx thickness, also decreasing proteinuria. Focal segmental glomerular sclerosis has no specific Food and Drug Administration-approved therapy currently, however, ERAs show promise in decreasing proteinuria and slowing tissue damage. ET-1 is a potential biomarker for autosomal dominant polycystic kidney disease progression and so it is thought that ERAs may be of some therapeutic benefit. KEY MESSAGES: Multiple studies have shown the utility of ERAs in CKD. These agents have shown to reduce blood pressure, proteinuria, and arterial stiffness. However, more clinical trials are needed, and the results of active or recently concluded studies are eagerly awaited.
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Raina et al. (2019) conducted a review in Chronic Kidney Disease. Endothelin receptor antagonists was evaluated. Endothelin receptor antagonists have shown utility in reducing blood pressure, proteinuria, and arterial stiffness in chronic kidney disease, though their clinical use is limited by fluid retention.
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