Targeting the Endothelin A Receptor in IgA Nephropathy
Donald E. Kohan, Jonathan Barratt, Hiddo J.L. Heerspink, Kirk N. Campbell, Mariannne Camargo, Ike Ogbaa, Ruth Haile-Meskale, Dana V. Rizk, Andrew King
Abstract
IgA nephropathy is the most common primary glomerulonephritis worldwide and carries a substantial risk of kidney failure. New agency-approved therapies, either specifically for IgA nephropathy or for chronic kidney disease in general, hold out hope for mitigating renal deterioration in patients with IgA nephropathy. 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 renoprotective in experimental models of, and reduces proteinuria in patients with, IgA nephropathy. This review discusses the evidence supporting the use of ETAR blockade in IgA nephropathy as well as addressing the potential role for this class of agents amongst the current and emerging therapies for treating this disorder.