Change in Kidney Function With Finerenone Doesn’t Impact Treatment’s Benefit

Heart failure patients treated with finerenone (Kerendia; Bayer AG) are more likely to have an early decline in kidney function than those treated with placebo, but the decline should not be construed as a sign to automatically stop the nonsteroidal mineralocorticoid receptor antagonist (MRA), a new analysis from FINEARTS-HF suggests.   

In the study, patients with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) treated with finerenone were more likely to experience a 15% or greater decrease in the estimated glomerular filtration rate (eGFR) at 1 month compared with placebo. But importantly, the early decline in kidney function was not associated with an increased risk of cardiovascular mortality or HF events.

By contrast, patients randomized to placebo who had evidence of declining renal function at 1 month had a higher risk of the cardiovascular death and HF outcomes.

“Although there was a much higher subsequent event rate for cardiovascular death and total HF events in placebo-treated patients experiencing an early decline in kidney function, this association was not seen or was not as strong in those assigned to finerenone,” write lead investigator Shingo Matsumoto, MD, PhD (University of Glasgow, Scotland), and colleagues in an analysis published January 13, 2025, in the Journal of the American College of Cardiology.

Michelle M. Kittleson, MD, PhD (Smidt Heart Institute at Cedars-Sinai, Los Angeles, CA), who wasn’t involved in the study, said worsening eGFR with numerous HF medications, including renin-angiotensin-aldosterone-system inhibitors, spironolactone, eplerenone, and sodium-glucose cotransporter 2 (SGLT2) inhibitors, is well documented.

Even with these drugs, the decline also is not associated with a diminished benefit. In fact, long-term outcomes are improved with these various medications.

“With the SGLT2 inhibitors, there’s initially a worsening in eGFR that then improves over time,” Kittleson told TCTMD. “There’s also data from ACE inhibitors and ARBs that even if there might be a decline in eGFR, kidney function is better preserved over time. The bottom line here is that we need to change the way we think about an increase in creatinine or transient worsening in eGFR.”

Kittleson emphasized that it’s important to interpret creatinine “bumps” or decreases in eGFR in clinical context. A decline in eGFR or increase in creatinine that is not clinically relevant shouldn’t lead to a “knee-jerk reflex to stop potentially lifesaving therapies,” she said.

“[If] the patient looks awesome, their fluid status is terrific, and their blood pressure is fine, just recheck to get another value, get another data point in the next month to see where things are going,” she said. “More likely than not, the kidney function will be the same or better and then you just let them live their life.”

Amanda Vest, MBBS (Cleveland Clinic, OH), another HF specialist who wasn’t involved in the study, also pointed out that several guideline-directed medical therapies (GDMT) for HF can cause an early decrease in eGFR. As such, these new data will help physicians who are beginning to use finerenone.

The bottom line here is that we need to change the way we think about an increase in creatinine or transient worsening in eGFR. Michelle M. Kittleson

“We ordinarily monitor the basic metabolic panel after initiation of new GDMT medications that can affect potassium and kidney function,” she told TCTMD. “On the one hand, it’s important, especially with the MRAs, to monitor potassium levels in the blood because of the possibility of high potassium, which can be dangerous. However, there is potential there for a clinician to see a minor change in kidney function and overreact with discontinuation of the medication.”

Like Kittleson, Vest said the FINEARTS-HF analysis—like a similar one with the MRAs eplerenone and spironolactone—provides reassurance that while there may be an initial decline with finerenone, it does not warrant stopping the medication.

“In fact, keeping the patient on that medication appears, from the data here, to benefit the patient over the subsequent months and years,” said Vest.

Decline in Kidney Function

In patients with HF with reduced ejection fraction (HFrEF), MRAs have been shown to improve clinical outcomes: the drug class today is included as one of the “four pillars” of GDMT. The TOPCAT study, which involved spironolactone, suggested that the benefit of MRAs extended to patients with HFpEF, but that trial was dogged with controversy.

FINEARTS-HF helped settle some of the outstanding questions, however. Presented in August at the European Society of Cardiology Congress and reported by TCTMD at that time, the study showed that finerenone reduced the risk of worsening HF outcomes and cardiovascular mortality in 6,001 patients with HFmrEF/HFpEF, a benefit driven largely by a reduction in the risk of worsening HF events.

Given the decline in eGFR seen with other agents, the researchers conducted a prespecified analysis to evaluate its occurrence with finerenone and to study its association with subsequent outcomes.

Overall, a decline in eGFR at 1 month —defined as a ≥ 15% reduction—occurred in 23.0% of patients treated with finerenone and 13.4% of those treated with placebo (P < 0.001). Reductions in eGFR ≥ 30% were also more frequent in finerenone-treated patients (4.9% vs 2.0%; P < 0.001), as was the proportion of patients experiencing an absolute ≥ 5 mL/min/1.73 m² reduction. Serum creatinine increases, measured either as a relative or absolute change from baseline to 1 month, were also more common in finerenone-treated patients.

In a landmark analysis focused on outcomes at 1 month and beyond, an early decline in eGFR was associated with a higher risk of cardiovascular mortality or worsening HF events compared with patients without worsening eGFR (RR 1.26; 95% CI 1.07-1.49). However, the decline in eGFR was associated with a higher risk of the study’s primary endpoint in the placebo group (RR 1.50; 95% CI 1.20-1.89) but not in the finerenone group (RR 1.07; 95% CI 0.84-1.39; P for interaction = 0.04 in the fully adjusted analysis).

No matter how an early decline in kidney function was defined, the primary study outcome was lower with finerenone than with placebo, say investigators. In fact, the effectiveness of finerenone was consistent across the range of absolute or percent changes in eGFR from baseline to 1 months, they add.

Blood Test Numbers in Context

With 13% of placebo-treated patients experiencing a decline in eGFR, the study also highlights how common it is to observe a decrease in kidney function in patients with HFmrEF/HFpEF, say researchers. This means that it’s easy to attribute any deterioration in kidney function to starting a new therapy.

“This could be highly disadvantageous for patients because an incidental decline in eGFR (ie, as seen with placebo) has very different implications than one induced by a drug such as finerenone (or other treatments like [an SGLT2] inhibitor or sacubitril/valsartan),” they write.

There is potential there for a clinician to see a minor change in kidney function and overreact with discontinuation of the medication. Amanda Vest

Kittleson said this new analysis should let physicians know they’re “doing the right thing” despite the lab results.

“Do not fear a small change in a lab test,” she said. “It does not mean that you are the proximate cause to the patient’s kidney failure. That’s not going to happen. It’s okay if there’s this initial decline in their eGFR because if it happens in the context of taking this medication, it explains they’re actually going to do well. This is not something to worry about.”  

Vest agreed that there is the potential for some physicians to see a minor change in kidney function and overreact by discontinuing the medication. She pointed out that many HF patients also have concomitant kidney conditions and staying on medication, despite the early drop in eGFR or bump in creatinine, is beneficial.

“We’re learning from studies that these medications prescribed to treat the heart failure are important not only in preventing cardiovascular mortality and heart failure hospitalizations, but they also have a role in helping to stabilize that kidney function longer term,” she said.

Despite the reassurances, Vest said there’s more to be known, particularly since there isn’t a lot of information available about when physicians should consider stopping some of these drugs.

“It would be high impact for further studies to be able to really define for the different medications what extent of eGFR deterioration is an indication to stop a medication,” she said. “It’s a hard question to answer in a blanket manner because there’s a lot of individualization and other factors, such as potassium [levels], blood pressure, and symptoms, but going forward it would be useful if the field were able to define those thresholds a little more precisely.”

In an editorial, Kevin Damman, MD, PhD (University Medical Center, Groningen, the Netherlands), says that from a practical perspective, measuring kidney function after starting nonsteroidal MRAs is still warranted because of the risk of a substantial decline in eGFR and hyperkalemia. Moreover, measuring kidney function allows doctors to uptitrate MRA therapy, which is often possible, he writes.