Endothelin Receptor Antagonists

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By Editorial Team

2 min read

Reviewed by: HU Medical Review Board | Last reviewed: June 2026 | Last updated: June 2026

Endothelin receptor antagonists (ERAs) are a newer group of prescription medicines for IgA nephropathy. They work by blocking endothelin, a substance in the body that tightens blood vessels. By blocking it, these medicines lower the pressure inside the kidney’s tiny filters and reduce the amount of protein leaking into your urine.1,2

How do they work?

In IgA nephropathy, high pressure in the kidney filters drives protein into the urine and adds to kidney damage. ERAs ease that pressure, which helps lower urine protein – one of the main goals of treatment.1,2

Which ERAs are FDA-approved for IgA nephropathy?

Two endothelin receptor antagonists are FDA-approved for IgA nephropathy in the United States:1,2

  • Sparsentan (Filspari®) – Approved to slow the decline in kidney function in adults with primary IgA nephropathy who are at risk of their disease getting worse. It blocks both endothelin and angiotensin receptors.
  • Atrasentan (Vanrafia®) – Approved (under accelerated approval) to reduce protein in the urine in adults with primary IgA nephropathy at risk of rapid progression.

Your doctor will discuss which option may fit you best.

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What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. For sparsentan (Filspari®), the most common side effects reported include:1

  • Higher potassium levels in the blood
  • Low blood pressure, including feeling dizzy when standing up
  • Swelling (fluid retention), often in the legs and feet
  • Dizziness
  • Anemia (a low red blood cell count)

These are not all the possible side effects of these medicines. Talk to your doctor about what to expect when taking an ERA. You also should call your doctor if you have any changes that concern you.

Other things to know

Sparsentan has a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because of the risk of liver injury (hepatotoxicity) and because it can cause serious harm to an unborn baby. Because of these risks:1

  • Sparsentan is available only through a restricted program called a REMS, and the health of your liver will be checked with blood tests before and during treatment.
  • Sparsentan must not be used during pregnancy. People who can become pregnant need to use effective birth control before, during, and for a short time after treatment.

Your care team will go over these requirements with you before you start.

Before beginning treatment for IgA nephropathy, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.

Talk to your doctor

ERAs are powerful tools for protecting the kidneys, but they require careful monitoring. Your doctor can explain whether one is right for you, what tests you will need, and what to watch for once you start.1,2

Treatment results and side effects can vary from person to person. This treatment information is not meant to replace professional medical advice. Talk to your doctor about what to expect before starting and while taking any treatment.