Risk Factors for the Initial Decline in Estimated Glomerular Filtration Rate (eGFR) Following Empagliflozin Therapy in Patients with Heart Failure reduced Ejection Fraction (HFrEF)

Heart failure is a long-term condition where the heart doesn’t pump blood as well as it should. It affects millions of people around the world and can lead to serious health problems, including damage to the kidneys. Heart failure can be measured by an Ejection fraction (EF), which shows how much blood the left ventricle (chamber responsible for pumping blood) pumps out with each contraction. EF is measured as a percentage. Heart failure with reduced ejection fraction (HFrEF) occurs when the heart muscle does not contract effectively and less oxygen-rich blood is pumped out to the body. A newer type of medication called sodium-glucose cotransporter 2 (SGLT2) inhibitors—such as empagliflozin—has been shown to help people with HFrEF live longer and stay healthier.

Empagliflozin works by helping the kidneys get rid of extra salt and water through urine. This can lower blood pressure and reduce the strain on the heart, which improves how well the heart functions—especially in people with heart failure.

However, doctors have noticed that soon after starting this medication, some patients experience a small drop in kidney function. This drop, called the “initial dip”, usually happens in the first one to two weeks of treatment and is measured by a test called estimated Glomerular Filtration Rate (eGFR), which checks how well the kidneys are working by evaluating how well they are filtering waste in the body.

We recently found that this initial dip is more common in older adults and in people who also have high blood pressure or diabetes (a condition where blood sugar is high). There is growing evidence that this early drop might not be harmful—in fact, it might even be a sign that the medication is helping protect the kidneys over time. But our earlier study was small, with only 123 patients, so more research is needed to understand if this dip is helpful or harmful in the long run.

In this project, we will study a much larger group of people who have HFrEF and are being treated with empagliflozin. We will look at two main things: first, which patients are most likely to experience the initial dip, and second, whether this dip has any lasting effect on their kidney health after six and twelve months. To do this, we will compare groups of patients—those who had an initial dip and those who didn’t—and use statistical tools to find patterns and predictors. These tools will help us understand which factors are linked to the dip and whether the dip is connected to better or worse kidney outcomes.

This research is important because it could help doctors know what to expect when starting patients on this medication. It may also help decide whether an early drop in kidney function is something to worry about or something that could actually mean the treatment is working. By learning more about this, we hope to improve care and protect kidney health in people living with chronic heart failure.