Diabetic kidney disease patients who take an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) may further improve excess albumin in the urine by adding finerenone, a new study finds.
Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, was compared with placebo in a randomized, double-blind trial of 821 diabetic nephropathy patients in 23 countries called the Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN). Investigators led by George L. Bakris, MD, of University of Chicago Medicine and Biological Sciences, compared the changes in patients’ urinary albumin-to-creatinine ratio (UACR) after 90 days of treatment with finerenone at various doses.
The researchers observed a dose-dependent reduction in the UACR for finerenone 7.5, 10, 15, and 20 mg daily, ranging from 21% to 38%, according to findings published in the Journal of the American Medical Association. Lower doses showed no decrease in albuminuria. To start, 36.7% of patients had very high albuminuria (UACR 300 mg/g or greater) and 40% had an estimated glomerular filtration rate of 30-60 mL/min/1.73m2.
Blood pressure was only modestly reduced over 3 months at the highest dosage of finerenone, however. Steroidal mineralcorticoid receptor antagonists have shown greater efficacy perhaps because they cross the blood-brain barrier and act centrally on receptors.
The risk of hyperkalemia was a major safety concern. It occurred in 2.1%, 3.2%, and 1.7% of patients taking finerenone doses 7.5, 15, and 20 mg, respectively, resulting in drug discontinuation. Serum potassium levels did not rise significantly in patients taking placebo. At baseline, no patients had a serum potassium concentration above 4.8 mmol/L and 60% had an eGFR above 60 mL/min/1.73 m2, putting them at lower risk of hyperkalemia.
About 73% of patients on ACE inhibitors or ARBs were taking above the minimum dosage of the drugs, including several taking above the maximum. Previous research on mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, have shown conflicting results on hyperkalemia.
The rate of adverse events and decreases in eGFR of 30% or more were similar in the placebo and finerenone groups. Serious, drug-related adverse events occurred in 1.5% of patients taking the drug.
“While the primary end point of ARTS-DN is CKD progression, and the study population was smaller with shorter follow-up than the previous trials, the significant reduction in UACR in patients receiving finerenone, combined with a safety profile similar to that in the placebo group, suggests that longer-term studies investigating clinical end points are warranted,” the investigators stated. Future trials also need to compare finerenone to other active medications.
The study was funded by Bayer HealthCare AG, the manufacturers of finerenone.