Targeting the Endothelin A Receptor in IgA Nephropathy

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and carries a substantial risk of kidney failure. New agency-approved therapies, either specifically for IgAN or for chronic kidney disease (CKD) in general, hold out hope for mitigating renal deterioration in patients with IgAN. The latest addition to this therapeutic armamentarium targets the endothelin-A receptor (ETAR). Activation of ETAR on multiple renal cell types elicits a host of pathophysiological effects, including vasoconstriction, cell proliferation, inflammation, apoptosis, and fibrosis. Blockade of ETAR is renopro-tective in experimental models of IgAN and reduces proteinuria in patients with IgAN. This review dis-cusses the evidence supporting the use of ETAR blockade in IgAN as well as addressing the potential role for this class of agents among the current and emerging therapies for treating this disorder. 2023 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).