Finerenone Also Slows Kidney Decline in Diabetes-Free Patients

Finerenone (Kerendia) slowed the decline of kidney function in adults with chronic kidney disease (CKD) who did not have diabetes, the large randomized FIND-CKD trial showed.

By month 32, the mean annual rate of change in estimated glomerular filtration rate (eGFR) was -3.3 mL/min/1.73 m² in the finerenone group and -4.0 mL/min/1.73 m² in the placebo group (P<0.001), reported researchers led by Hiddo Heerspink, PhD, of the University Medical Center Groningen in the Netherlands.

The treatment benefit — a difference of 0.7 mL/min/1.73 m² versus placebo — matched the level of eGFR slowing previously seen in CKD patients with diabetes, according to findings reported in the New England Journal of Medicine and simultaneously presented at the European Renal Association annual congress in Glasgow, Scotland.

“The magnitude of the effect of finerenone in the current trial was similar to the magnitude previously reported with other kidney-protective drugs, including RAS inhibitors and SGLT2 inhibitors, which reduced the annual rate of decline in the eGFR by 0.5 to 1.0 mL/min/1.73 m²,” Heerspink and co-authors wrote.

“The reduction in the mean annual rate of change in the eGFR from baseline to month 3 with finerenone suggests that the total eGFR slope may be an underestimate because finerenone, by means of its mechanism of action, initially decreases the eGFR,” they added.

Additionally, risk for a composite of kidney or cardiovascular events (an eGFR reduction of at least 57%, kidney failure, hospitalization for heart failure, or death from cardiovascular causes) was 23% lower with finerenone (HR 0.77, 95% CI 0.60-0.99, P=0.04).

A composite of the two kidney events also favored finerenone (HR 0.78, 95% CI 0.60-1.01), as did a composite of the two cardiovascular events (HR 0.60, 95% CI 0.27-1.33), though statistical significance wasn’t reached.

The nonsteroidal mineralocorticoid receptor antagonist was approved for slowing CKD progression in type 2 diabetes in 2021. It has since also picked up an indication to treat adults with heart failure with mildly reduced ejection fraction or preserved ejection fraction.

“Although type 2 diabetes is the most common cause of CKD, more than half the cases are in persons without diabetes,” the authors noted.

Current guidelines recommend the use of RAS inhibitors and SGLT2 inhibitors in adults with CKD, regardless of whether they have diabetes. Despite these treatments, progressive loss of kidney function and adverse cardiovascular outcomes remain common in CKD patients.

The randomized trial randomized 1,584 diabetes-free adults using a RAS inhibitor with albuminuria and an eGFR between 25 and 90 mL/min/1.73 m². Half received 10 or 20 mg of daily finerenone, and half received a placebo.

At baseline, the average eGFR was 46.8 mL/min/1.73 m² in the finerenone group and 46.6 mL/min/1.73 m² in the placebo group.

About 17% of trial participants were using SGLT2 inhibitors at baseline; the efficacy of finerenone was similar in participants using and not using these agents. “Although we hypothesize that the use of both finerenone and SGLT2 inhibitors may provide complementary effects, this was not directly tested in the present trial,” the researchers noted.

Hyperkalemia was the most common adverse event, occurring in 17% of those on finerenone and 13.3% on placebo. As a result, 12 participants on finerenone and one on placebo discontinued the trial regimen, while seven and five participants were hospitalized, respectively.

FIND-CKD investigators also assessed outcomes specifically in patients with CKD due to glomerular diseases, who made up 57% of the cohort.

In this prespecified exploratory subgroup analysis published in JAMA, the total eGFR slope up to 32 months was -3.50 mL/min/1.73 m² per year with finerenone and -4.23 mL/min/1.73 m² per year with placebo, reported Brendon Neuen, MBBS, MSc, PhD, of the George Institute for Global Health in Sydney, and colleagues.

Finerenone also reduced albuminuria at month 12 by 42% and lowered the risk of kidney failure or an eGFR decline of 40% or more compared with placebo (7.42 vs 9.60 events per 100 patient-years; HR 0.74, 95% CI 0.57-0.97) in this population.

“Notably, these benefits were consistent irrespective of glomerular disease subtype and SGLT2 inhibitor use, with a similar magnitude of benefit observed for all outcomes in analyses restricted to biopsy-proven cases of glomerular diseases,” wrote Neuen and co-authors. “These findings are clinically important because glomerular diseases are a leading cause of kidney failure, and many glomerular disease subtypes have few specific treatments available.”

Of these 903 participants, 46.1% had investigator-reported immunoglobulin A nephropathy, 23.8% had focal segmental glomerulosclerosis, and 10% had membranous nephropathy. The average age was 51 years, 40% were female, and 62% were Asian. Mean baseline eGFR was 48.8 mL/min/1.73 m² and the median urinary albumin-to-creatinine ratio was 839.6 mg/g.

Participants with certain kidney diseases were excluded, thereby limiting the scope of the findings. Among those left out of the trial were individuals with autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis, antineutrophil cytoplasmic antibody-associated vasculitis, extremely low eGFR, or low-level albuminuria.