Efficacy and safety of aldosterone synthase inhibition with and without empagliflozin for chronic kidney disease: a randomised, controlled, phase 2 trial

Global Kidney Trials Insights: A guide for Everyone

Efficacy and safety of aldosterone synthase inhibition with and without empagliflozin for chronic kidney disease: a randomised, controlled, phase 2 trial

Global Kidney Trials Insights: A Guide for Everyone

1. The question for investigation?

Simply put, scientific investigators wanted to know: Does the medication BI 690517 reduce the amount of protein in the urine of kidney patients?

This international study is looking at a new medication called BI 690517 to treat chronic kidney disease (CKD). Chronic kidney disease is a condition where your kidneys get worse over time, at varying rates. Many people with chronic kidney disease take medications called ACE inhibitors or ARBs, but these don’t always work perfectly. BI 690517 works differently – it lowers levels of a hormone called aldosterone, which can damage kidneys.

The study involved over 500 people with chronic kidney disease who were already taking ACE inhibitors or ARBs. Half the people were given a sugar pill (placebo) for eight weeks, then either another placebo or BI 690517 at different doses for fourteen weeks. The other half got a medication for diabetes called empagliflozin along with the placebo or BI 690517.

The main thing the researchers were looking at was how much protein was in the participants’ urine. Too much protein in the urine is a sign of kidney damage and lowering the amount of protein in urine allows to protect patients from negative events such as cardiovascular fatal and non-fatal events, mortality and progression of chronic kidney disease to the final stage that needs dialysis.

2. The findings of the study

Authors found that the people who took BI 690517 had a bigger decrease in protein in their urine than those who took the placebo. This effect got stronger as the dose of BI 690517 increased. Taking BI 690517 with empagliflozin seemed to work just as well as taking it alone. An important side effect to watch for with BI 690517 is high potassium levels in the blood. This happened more often in the people taking BI 690517 than those taking the placebo, but it usually didn’t require any treatment. A few people taking BI 690517 also had problems with their adrenal glands, which are small glands that sit on top of the kidneys. No one died during this study. This is a promising early study, but BI 690517 is still being tested. More research is needed to see if it is safe and effective in the long term (i.e. after many years of therapy). If future studies are positive, BI 690517 could be a new treatment option for people with chronic kidney disease. The outcome of this study is that BI 690517, a new medication, seems to be effective in reducing protein in the urine of people with chronic kidney disease. This could be helpful in slowing down the progression of the disease.

Here are some key takeaways:

  • BI 690517 seems to work well on its own and seems to work even better when taken with another medication for diabetes called empagliflozin.
  • An important side effect to watch for is high potassium levels, but this can be managed in most cases.
  • This is a promising early study, but more research is needed to see if this medication is safe and effective in the long term.
  • If future studies are positive, BI 690517 could be a new treatment option for people with chronic kidney disease.

Some limitations to keep in mind:

  • The study only lasted a short time, so we don’t know yet how safe and effective this medication is over a longer period.

This edition was edited by Michele Provenzano, ISN-ACT Global Trials Focus team member and Duane Sunwold, ISN-ACT Patient Engagement in Renal Trials subgroup member, supported by members of the ISN Patient Engagement in Renal Trials subgroup and members of the Patient Liaison Advisory Group.

Glossaries

Read the GTF editorial team’s original review of the BEST-Fluids trial here.
Access the complete study here.
Any questions? Contact us at research@theisn.org

Glossaries

Adrenal glands are small glands that sit on top of the kidneys.

Efficacy refers to how well a medication or treatment works in achieving its intended effect.

Aldosterone is a hormone produced by your adrenal glands, which sit on top of your kidneys. It's kind of like a chemical messenger that helps regulate the amount of water and salt in your body.

Semaglutide is a medication used to treat type 2 diabetes and help with weight loss. It works by mimicking a hormone (called GLP-1) in the body that helps control blood sugar and appetite. It's usually given as an injection.

Random assignment (or randomisation) is a way of putting people into different groups in a study by chance, like flipping a coin. This helps make sure the groups are similar at the start of the study, so researchers can better tell if a treatment is really working.

Cardiovascular disease refers to diseases that affect the heart and blood vessels. This includes problems like heart attacks, strokes, and heart failure. Diabetes, high cholesterol, high blood pressure, and being overweight can damage the blood vessels and cause cardiovascular disease.

refers to the best way to take care of patients

refers to an event over time that is measured to monitor the impact of a treatment in a given population.

Delayed graft function happens when a transplanted kidney does not start working right away and needs additional support with dialysis to help remove excess fluid and waste from the blood, Delayed graft function can be linked to several problems, including the need for ongoing dialysis until the kidney works well enough, longer hospital stays, a higher risk of kidney failure, and death.

This contains the electrolytes commonly found in our bodies. It has extra minerals like potassium and magnesium that are important to help keep our bodies healthy.

It contains primarily salty water. It is commonly used during and early after the transplant surgery; and

Arteriovenous fistula (AVF): irregular connection between an artery and a vein

Hemodiafiltration, is combining this process with direct fluid removal by adding many tiny holes, also called pores, to the membrane. These pores allow fluid and waste to be passed through more easily, including larger wastes that might not otherwise be removed through dialysis. As this process involves much more fluid being removed, some replacement waste-free fluid is added to the filtered blood before it returns to the body. It is unclear if this approach improves heart health and survival. 

In hemodialysis, wastes are removed from the blood by travelling through a barrier (called a membrane) in the filter of the dialysis machine, which allows wastes to pass through but aims to keep important parts of the blood, like blood cells and protein, in the bloodstream. One challenge of this approach is that some larger wastes (called middle-molecular-weight molecules), do not pass through the barrier very well. The build-up of these wastes may increase the risk of health problems, including for heart health.