Endothelin A Receptor Antagonist

Endothelin A receptor antagonist is a medication used to reduce protein excretion in urine (proteinuria) in adults with primary immunoglobulin A (IgA) nephropathy. Endothelin A receptor antagonist works by preventing endothelin 1, a protein particle (peptide) from binding to endothelin A receptors and activating them.

Primary immunoglobulin A nephropathy, also known as Berger’s disease is an autoimmune disorder, where the body’s own immune system attacks the kidneys. Clumps of immunoglobulin A, a type of antibodies get deposited in the kidneys, causing inflammation and kidney damage, resulting in leakage of blood and protein in the urine.

Endothelin 1 is a peptide produced by cells in the inner lining (endothelium) of blood vessels, the smooth muscles around them, kidneys, and some immune cells (macrophages). Endothelin 1 constricts blood vessels, and has pro-inflammatory properties. It is responsible for regulating blood pressure and fluid balance in the body.

High levels of endothelin 1 increases blood pressure, reduces blood flow to the kidneys, and increases reabsorption of water and sodium in the kidneys, leading to fluid retention. Endothelin 1 is believed to contribute to the inflammation and damage in primary IgA nephropathy, and resultant proteinuria.

Endothelin 1 works by binding to endothelin receptors, and endothelin A receptor antagonist blocks the interaction between endothelin 1 and endothelin A receptors. This reduces blood pressure, inflammation and proteinuria.

Currently, atrasentan (Vanrafia) is the only drug in this class approved by the FDA to treat proteinuria in adults with primary IgA nephropathy. The drug has received accelerated approval in April 2025, because it showed reduction of proteinuria in clinical trials. Continued approval will depend on results of further clinical trials that prove that the drug slows down progression of disease and decline in kidney function.

Endothelin A receptor antagonist is an oral tablet used to reduce proteinuria in adults with primary immunoglobulin A nephropathy, who are at risk for rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) that is 1.5 g/g or higher.

Common side effects of endothelin A receptor antagonist include the following:

• Fluid retention
• Swelling of extremities (peripheral edema)
• Anemia
• Toxicity to the lever
• Increase in liver transaminase enzymes ALT and AST
• Decrease in hemoglobin
• Low blood pressure (hypotension)
• Reduced sperm count
• Toxicity to the embryo/fetus

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of FDA-approved endothelin A receptor antagonist include:

• atrasentan
• Vanrafia