Episode Overview:
Donald Kohan, PhD is an Emeritus Professor at the University of Utah Health with expertise in endothelin receptors, sodium transporters, and the renin-angiotensin-aldosterone system in chronic kidney disease.
In this episode, Professor Kohan provides an overview of the endothelin system and how it relates to the pathophysiology of chronic kidney disease and IgA nephropathy specifically.
Key Quotes:
- “Endothelin 1 is a really unusual molecule. It's highly stable because it has 2 interchain disulfide bonds that resist degradation. It's extremely potent having about 10 fold higher potency than any other known vasoactive factor.”
- “Angiotensin and ET-1 cause their effects through different pathways.”
- “Angiotensin stimulates transient calcium release, which causes more short-term contraction and other effects. While endothelin 1 stimulates more sustained calcium release, which then elicits longer lasting pathophysiologic effects.”
Key Takeaways:
- (04:41) Endothelin-1 acts via ETA receptors to cause vasoconstriction, fibrosis, cell proliferation and other effects that promote chronic kidney disease
- (06:15) The endothelin and renin-angiotensin systems interact, forming a vicious cycle that worsens kidney injury
- (12:19) In IgA nephropathy models, combined ETA + angiotensin receptor blockade with sparsentan reduced proteinuria and kidney injury more than angiotensin blockade alone
