Finerenone in Chronic Kidney Disease Without Diabetes

Key Takeaways

• Finerenone was associated with slower eGFR decline than placebo over 32 months.
• The prespecified kidney-or-cardiovascular composite was lower with finerenone, while kidney-only and cardiovascular-only composites were numerically favorable but did not meet conventional statistical significance.
• Hyperkalemia was the most common adverse event and more often led to treatment discontinuation with finerenone.

In the NEJM trial, finerenone slowed annual eGFR decline to −3.3 ml per minute per 1.73 m2 over 32 months, versus −4.0 with placebo. The between-group difference was 0.7 ml per minute per 1.73 m2 per year (95% CI, 0.3 to 1.1; P<0.001). The comparison involved adults with chronic kidney disease without diabetes who were receiving background renin–angiotensin system inhibitors. Finerenone was associated with slower kidney-function decline than placebo in this population.

The FIND-CKD trial randomly assigned 1,584 adults without diabetes who had chronic kidney disease, with 793 assigned to finerenone and 791 to placebo. Eligibility required an eGFR of 25 to less than 90 ml per minute per 1.73 m2, a urinary albumin-to-creatinine ratio of 200 to ≤3500 (with albumin in milligrams and creatinine in grams), and background renin–angiotensin system inhibitor use. Participants received finerenone at 10 or 20 mg daily or matching placebo, and mean baseline eGFR was 46.8±16.2 and 46.6±16.0 ml per minute per 1.73 m2, respectively. The primary outcome was total eGFR slope from baseline to month 32, assessed with a two-slope linear spline mixed-effects model, to track kidney-function decline over the 32-month follow-up.

Beyond the primary slope endpoint, prespecified hierarchical testing identified a lower risk for the composite kidney-or-cardiovascular outcome with finerenone than with placebo. The hazard ratio for that outcome was 0.77 (95% CI, 0.60 to 0.99; P=0.04). The kidney-only composite was numerically lower with finerenone than placebo, with a hazard ratio of 0.78 (95% CI, 0.60 to 1.01). The cardiovascular-only composite also numerically favored finerenone, with a hazard ratio of 0.60 (95% CI, 0.27 to 1.33). These findings extended beyond eGFR slope to the prespecified composite outcome, while the component composites remained numerically favorable but were not clearly statistically significant.

The main safety signal was hyperkalemia, the most common adverse event in both study groups. Hyperkalemia occurred in 135 participants (17.0%) with finerenone and 105 participants (13.3%) with placebo. These events led to discontinuation of the trial regimen in 12 participants (1.5%) and 1 participant (0.1%), respectively. Hyperkalemia-related hospitalization occurred in 7 participants (0.9%) with finerenone and 5 participants (0.6%) with placebo. Slower kidney-function decline and lower prespecified kidney-or-cardiovascular risk were accompanied by more hyperkalemia-related treatment interruption with finerenone than with placebo.