What is the role of endothelin antagonists in the management of proteinuria?

Updated: Mar 25, 2020
  • Author: Beje Thomas, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

Renal inflammation and fibrosis has been associated with endothelin activation. Endothelin A (ETA) receptor activation leads to vasoconstriction in vascular smooth muscle. ETA blockade leads to dilation of the glomerular capillaries, decreasing the permeability of  albumin. Endothelin B (ETB) decreases arterial pressure by inhibiting salt and water reabsorption in the kidneys. A trial of an experimental ETA-selective antagonist, avosentan, in patients with diabetic nephropathy showed a decrease in albuminuria, but with adverse effects including fluid retention and heart failure exacerbation. Atrasentan, another experimental ETA antagonist with a better adverse effect profile than avosentan, has also been shown to reduce proteinuria. [46, 47]


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