Combining the novel mineralocorticoid receptor antagonist (MRA) balcinrenone with the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin was superior to dapagliflozin monotherapy in reducing albumineria in patients with chronic kidney disease (CKD), according to the results of a new study.

“We found that 12 weeks of treatment with balcinrenone at either 15 milligrams or 40 milligrams, combined with dapagliflozin 10 milligrams, significantly reduced urinary albumin to creatinine ratio compared to dapagliflozin alone in people with CKD Stage III to IV,” said study author Patrick Mark, MB, ChB, PhD, professor of nephrology at the University of Glasgow. “These patients with significantly advanced CKD are at risk of progression to kidney failure, and the results were consistent across all sub-groups that that included type 2 diabetes status, baseline eGFR, baseline urine albumin-to-creatinine ratio and use of SGLT-2 inhibitors.”

The results were presented at Kidney Week 2025 and published simultaneously in the Lancet, to coincide with the meeting.

Dr Mark explained that even with advances in care for people with CKD, particularly with SGLT-2 inhibition, there continues to be a high residual risk of progression towards kidney failure. “We know that albuminuria is one of the most important markers of progression, and it's amenable to intervention, and we know that across the class of mineralocorticoid receptor antagonists, which target aldosterone, they reduce albuminuria,” he said. “But one of the concerns with this class of drugs is the propensity to cause hyperkalemia, or high serum potassium.”

Pre-clinical data suggests that balcinrenone may be less likely to cause hyperkalemia than other agents. In this study, Dr. Mark and colleagues assessed the efficacy and safety of balcinrenone combined with dapagliflozin in a phase 2 randomized controlled trial. The primary efficacy endpoint was relative change in urinary albumin to creatinine ratio (UACR) from baseline to week 12, and secondary endpoints included safety and tolerability.

A total of 324 adults with CKD were randomly assigned to receive balcinrenone 15 mg plus dapagliflozin 10 mg (n=108), balcinrenone 40 mg plus dapagliflozin 10 mg (n=110), or dapagliflozin plus placebo (n=106). The mean age of the cohort was 64.6 years and they had a mean eGFR of 42.2 mL/min per 1.73 m2, median UACR of 365 mg/g, and 56% were taking SGLT2 inhibitors.

Both doses of balcinrenone combined with dapagliflozin were superior in reducing UACR compared with dapagliflozin monotherapy throughout the 12 week period. At the end of the study period, the UACR difference versus dapagliflozin was –22·8% (p=0·0038) for balcinrenone 15 mg and –32·8% (p<0·0001) for balcinrenone 40 mg.

“Balcinrenone in either dose led to a significant reduction in albuminuria, and there was a dose dependent response with the albuminuria reduction of 23% and 33%,” said Dr. Mark. “The primary endpoint of the trial was met, and the combination was safe and well tolerated. We had very few patients leaving the trial.”

Investigator-reported adverse events of hyperkalaemia were observed in 6% of the group receiving 15 mg of balcinrenone, 7% in the balcinrenone 40 mg group, and 5% of the dapagliflozin monotherapy group. Other adverse events included hypotension and renal events, but they were few and balanced across the three cohorts. There were two deaths during the study, but both occurred more than 28 days after the last drug dose was given.

“Overall, the combination of balcinrenone and dapagliflozin was safe and well tolerated, with minor effects on serum potassium, even in advanced CKD,” said Dr. Mark. “And certainly, this merits further study.”

The study was sponsored by Astrazeneca

SA-OR087 Efficacy and Safety of Balcinrenone in Combination with Dapagliflozin on Albuminuria in Participants with CKD – Presented at: Kidney Week 2025; November 5-9, 2025; Houston

Heerspink, HJL, Cardona JF, Shivinder J et al. Balcinrenone in combination with dapagliflozin compared with dapagliflozin alone in patients with chronic kidney disease and albuminuria: a randomised, active-controlled double-blind, phase 2b clinical trial. The Lancet, Online firstNovember 08, 2025

Illustration by April Brust