Finerenone Reduces Albuminuria in Diabetic Nephropathy

Finerenone, a new nonsteroidal mineralocorticoid receptor antagonist, can improve albuminuria in patients with diabetic kidney disease, reports a trial in the Journal of the American Medical Association.

The randomized controlled trial included 823 patients with type 2 diabetes; persistent albuminuria, urinary albumin–creatinine ratio (ACR) 30 mg/g or higher; and current treatment with a renin-angiotensin system (RAS) blocker. The mean age was 64.2 years, and 78 percent of patients were men. The baseline ACR was 300 mg/g or higher in 36.7 percent of patients, and 40.0 percent had an estimated GFR of 60 mL/min/1.73 m2 or less.

The patients were assigned to treatment with oral finerenone, in doses ranging from 1.25 to 25 mg/d, or placebo, while continuing their RAS blocker. The changes in urinary ACR at 90 days were compared between groups. Serum potassium level and kidney function were assessed as safety outcomes.

Finerenone reduced ACR in a dose-dependent fashion. The placebo-corrected mean ratio of ACR at 90 days (compared with baseline) was 0.79 with finerenone at a dose of 7.5 mg/g, 0.76 at 10 mg/d, 0.67 at 15 mg/d, and 0.62 at 20 mg/d. At the 10 mg/d dose, there was no difference in the rate of hyperkalemia leading to treatment discontinuation in comparison with placebo. The rates of this safety outcome were 2.1 percent with finerenone at a dose of 27.5 mg/d, 3.2 percent at 15 mg/d, and 1.7 percent at 20 mg/d. There were no differences in the rate of a 30 percent or greater drop in estimated GFR or in serious adverse events.

Adding a steroid mineralocorticoid receptor antagonist to a RAS blocker reduces proteinuria in patients with chronic kidney disease, but with a high risk of adverse events. A previous trial found that finerenone decreased albuminuria in patients with CKD and heart failure, with a lower rate of hyperkalemia in comparison with spironolactone.

This placebo-controlled trial shows a reduction in urinary ACR in patients with diabetic nephropathy assigned to finerenone, added to a RAS blocker. Further trials of finerenone are needed, including comparison with other active treatments [Bakris GL, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy. JAMA 2015; 314:884–894].