Non-steroidal mineralocorticoid receptor antagonists (nsMRAs)

Non-steroidal mineralocorticoid (pronounced: min-er-al-oh-KOR-tuh-koyd) receptor antagonists are a type of oral (taken by mouth) prescription medicine used for some people with kidney disease. They are commonly referred to as “nsMRAs”.

There is only one nsMRA available for use in the US – finerenone (Kerendia). The FDA approved this medicine in 2021. Other nsMRAs are currently being developed and going through clinical trials.

The nsMRAs are considered “kidney protection” medicines – they can help keep your glomeruli (small filters in your kidneys) healthy and lower your urine albumin-creatinine ratio (uACR) levels. They can also lower your risk of cardiovascular disease (CVD, including heart failure, heart attack, or stroke).

Finerenone is only FDA-approved for people with chronic kidney disease and type 2 diabetes. The effects of nsMRAs in people without diabetes are being tested in clinical trials.

The nsMRAs work by lowering the effects of aldosterone in the body. Aldosterone is a hormone made by your body that helps balance your blood pressure. When your blood pressure starts to go too low, the body makes aldosterone to help bring it up.

The main way aldosterone works is by telling your kidneys to keep extra sodium (salt) and water in the body. Usually, the kidneys help remove extra sodium and water from the body. When there is too much aldosterone, your kidneys try to keep the extra sodium and water inside your body. This can cause high blood pressure and/or kidney damage. It can also make heart failure worse.

Taking an nsMRA can help lower the amount of extra sodium and water in your body. This will help lower the amount of stress on your kidneys and heart.

In clinical trials, people with chronic kidney disease (CKD) and type 2 diabetes who took an nsMRA (usually added to an ACE inhibitor or ARB) saw many kidney health benefits, including:

• slower progression (worsening) of chronic kidney disease (CKD)
• lower risk of kidney failure
• lower risk of heart attack, stroke, or heart failure exacerbation (flare-up)

• lower uACR level for people with albuminuria

Hyperkalemia (high potassium levels)

The nsMRAs can raise the level of potassium in your blood. This can cause hyperkalemia (high potassium levels). Your doctor will likely check your potassium levels before you start this medicine and again a few weeks after. Be sure to complete your blood tests as recommended by your doctor. The nsMRA may need to be stopped or the dose may need to be lowered if your potassium levels go too high.

Low blood pressure

The nsMRAs have not been shown in clinical trials to lower blood pressure in most people. Individual results may vary so it is still good to be aware of this possible side effect. Symptoms of low blood pressure include feeling weak, dizzy, or lightheaded. These can be worse when standing up or changing positions. Another symptom of low blood pressure is fatigue (feeling tired). If you have any of these symptoms, talk with your doctor.

Importance of completing blood tests

Your doctor will likely need you to complete blood tests to make sure this medicine stays safe for you. This is most important after starting the medicine or after any dose changes. These blood tests include checking your estimated glomerular filtration rate (eGFR) and potassium level. Be sure to complete your blood tests as recommended by your doctor.

Drug interactions

Grapefruit and grapefruit juice contain an ingredient that can slow the breakdown of finerenone (an nsMRA) in your body. This can lead to unsafe drug levels in your blood. It is best to avoid eating grapefruit or drinking grapefruit juice while taking finerenone.

Comparing to other MRAs

Although the nsMRA class of medicines is new, steroid based MRAs have been available in the US for decades. These include:

• Spironolactone (Aldactone) – commonly used to treat heart failure or high blood pressure. It can also be used to lower uACR levels for people with albuminuria.
• Eplerenone (Inspra) – mainly used to treat heart failure

These medicines are both available as generic options. Compared to the nsMRAs, the steroid based MRAs have a higher risk of causing hyperkalemia (high potassium levels). This risk is increased even more in people with chronic kidney disease and with lower eGFR levels.

• When should I get blood tests done after I start this medication to check my potassium and eGFR?
• When was the last time my potassium level was checked?
• Should I be aware of any drug interactions between finerenone and the other medicines I am taking?

• Kidney Numbers and the CKD Heat Map