The dual pathway
Endothelin-1 (ET-1) and angiotensin II (ANG II) both play fundamental roles in the pathophysiology of kidney diseases such as IgAN1–4
They act in tandem via their receptors ETAR and AT1R to amplify underlying disease damage and compromise the glomerular filtration barrier, leading to a progressive loss of kidney function1–11
The impact of ET-1 and ANG II on pathophysiology and disease progression of IgAN
The combined effect of ET-1 and ANG II increases the rate of progression to kidney failure1-4,6-11
A: ANG II increases ET-1 activity & ET-1 increases ANG II activity
Adapted from Komers R, Plotkin H, 20161
References & footnotes
Abbreviations
ANG II, angiotensin II; AT1R, angiotensin II receptor type 1; ECM, extracellular matrix; ET-1, endothelin-1; ETAR, endothelin A receptor; IgA, immunoglobulin A; IgAN, IgA nephropathy.
References
- Komers R, Plotkin H. Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease. Am J Physiol Regul Integr Comp Physiol. 2016;310:R877–84.
- Kohan DE, Barton M. Endothelin and Endothelin Antagonists in Chronic Kidney Disease. Kidney Int. 2014;86:896-904.
- Raina R, et al. The Role of Endothelin and Endothelin Antagonists in Chronic Kidney Disease. Kidney Dis. 2020;6:22–34.
- Siragy H, Carey R. Role of the Intrarenal Renin-Angiotensin- Aldosterone System in Chronic Kidney Disease. Am J Nephrol. 2010;31:541–50.
- Lai KN, et al. IgA Nephropathy. Nat Rev Dis Primers. 2016;2:16001.
- Lehrke I, et al. Renal Endothelin-1 and Endothelin Receptor Type B Expression in Glomerular Diseases with Proteinuria. J Am Soc Nephrol. 2001;12(11):2321–9.
- Chan LY, et al. Tubular Expression of Angiotensin II Receptors and Their Regulation in IgA Nephropathy. J Am Soc Nephrol. 2005;16(8):2306–17.
- Benigni A, et al. Endothelin-targeted new treatments for proteinuric and inflammatory glomerular diseases: focus on the added value to anti-renin-angiotensin system inhibition. Pediatr Nephrol. 2021;36(4):763–75.
- Lin YJ, et al. Angiotensin II enhances endothelin-1-induced vasoconstriction through upregulating endothelin type A receptor. Biochem Biophy Res Commun. 2014;451:2639.
- Kohan DE, et al. Physiology of endothelin and the kidney. Compr Physiol. 2011;1(2):883–919.
- Sharma S, Smyth B. From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options. Kidney Blood Press Res. 2021;46(4):411–20.
HQ-SPT-2500016 | Date of preparation: February 2025