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

doi:10.1016/j.ekir.2023.07.023

Targeting the Endothelin A Receptor in IgA Nephropathy

Kidney Int Rep. 2023 Aug 4;8(11):2198-2210. doi: 10.1016/j.ekir.2023.07.023. eCollection 2023 Nov.

Authors

Donald E Kohan¹, Jonathan Barratt², Hiddo J L Heerspink³, Kirk N Campbell⁴, Mariannne Camargo⁵, Ike Ogbaa⁵, Ruth Haile-Meskale⁵, Dana V Rizk⁶, Andrew King⁵

Affiliations

¹ Division of Nephrology, University of Utah Health, Salt Lake City, Utah, USA.
² Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
³ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
⁴ Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Chinook Therapeutics, Seattle, Washington, USA.
⁶ Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Abstract

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 (ET_AR). Activation of ET_AR on multiple renal cell types elicits a host of pathophysiological effects, including vasoconstriction, cell proliferation, inflammation, apoptosis, and fibrosis. Blockade of ET_AR is renoprotective in experimental models of IgAN and reduces proteinuria in patients with IgAN. This review discusses the evidence supporting the use of ET_AR 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.

Keywords: IgA nephropathy; antagonist; endothelin; kidney; proteinuria; receptor.

Publication types

Review