Mineralocorticoid receptor antagonists (MRAs) are often used with a renin-angiotensin system (RAS) blocker to further reduce proteinuria in patients with CKD. However, eplerenone and spironolactone increase the risk of hyperkalemia in these patients. Finerenone (BAY94-8862) is a new nonsteroidal MRA that has better receptor selectivity than spironolactone, associating with lower incidence of hyperkalemia, and better receptor affinity than eplerenone in vitro, providing a greater reduction in proteinuria and end-organ damage.
MRA Tolerability Study-Diabetic Nephropathy (ARTS-DN) was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2B study, designed to compare the efficacy and safety of various oral doses of finerenone and placebo in patients with type 2 diabetes mellitus (T2DM) and persistent albuminuria. Persistent albuminuria is defined as urinary albumin-creatinine ratio (UACR) of 330 mg/g. These participants would be assigned finerenone 1.25 to 20mg once daily along with a RAS blocker (ACEI or ARB) for 90 days. The primary outcome of the study was the ratio of UACR at day 90 compared to baseline.
The secondary outcome was of safety and monitoring adverse events, which includes incidence of hyperkalemia, a change in systolic blood pressure, and a decrease in ³30% in estimated glomerular filtration rate (eGFR). The study spanned from June 2013 to August 2014. Of the 1,501 patients who were screened and randomized, 821 patients received the study drug, and 764 patients completed treatment. Prior to study, the serum potassium level was monitored and corrected so that the participants’ values were within normal range.
From baseline to day 90, compared to the placebo group, the finerenone groups had a dose-dependent reduction in UACR. The mean ratios of UACR for finerenone groups of:
- 7.5 mg/day was 0.79 (90% CI, 0.68-0.91; p = 0.004)
- 10 mg/day was 0.76 (90% CI, 0.65-0.88; p = 0.001)
- 15 mg/day, 0.67 (90% CI, 0.58-0.77; p < 0.001); and
- 20 mg/day was 0.62 (90% CI, 0.54-0.72; p < 0.001)
A 50% decrease of UACR from baseline to day 90 was observed in 13.6% of patients in the placebo group and in 17.2%, 17.2%, 33.6%, and 40.2% in the finerenone 7.5-, 10-, 15-, and 20 mg/day groups, respectively.
There was no difference in the overall occurrences of adverse events between the finerenone groups and the placebo group. Hyperkalemia was not seen in the placebo group along with the finerenone 10 mg/day group. However, finerenone was discontinued in 12 out of 821 patients (1.5%) due to an increase in serum potassium of at least 5.6 mmol/L. Incidences of hyperkalemia leading to discontinuation were observed in finerenone 7.5-, 15-, and 20-mg/day groups at 2.1%, 3.2%, and 1.7%, respectively. Incidences of an eGFR decrease of > 30% were similar in the placebo group compared to the finerenone groups. However, at baseline, 60% of patients had an eGFR of above 60 mL/min/1.73m2, making them have lower risk of hyperkalemia. Furthermore, from baseline to day 90, there was no correlation across all treatment groups between the ratio of UACR and the change in systolic blood pressure or change in eGFR.
The authors concluded that among patients with diabetic nephropathy who are on an ACEI or an ARB, adding on finerenone resulted in improvements of UACR compared to placebo. However, the short duration of the study does not allow for monitoring of long term effects of finerenone on CKD progression. Therefore further studies are warranted to determine the efficacy and safety of finerenone with other active medications.
- Finerenone is a new nonsteroidal MRA that provides a greater reduction in proteinuria and end organ damage, and has lower incidence of hyperkalemia.
- No difference was observed in the overall incidents of serious adverse events in the placebo vs. finerenone groups.
- Patients with diabetic nephropathy who are on ACEI or ARB can benefit from taking finerenone to improve UACR to reduce CKD progression.
Bakris GL, Agarwal R, Chan JC, et al. “Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial.” JAMA. 2015;314(9):884-894. doi:10.1001/jama.2015.10081.